Name: subcutaneous trigeminal nerve field stimulation for refractory facial pain
Uploaded: 2017-05-10T13:00:00
Description: Watch this Scientific Journal Video about Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain at JoVE.com

This work was in part supported by the Collaborative Research Center 1158 (SFB1158 From nociception to chronic pain: Structure-Function properties of neural pathways and their reorganization), funded by the DFG (Deutsche Forschungsgemeinschaft).

NOTE: All procedures are performed as individual healing attempts (&#34;Individueller Heilversuch&#34;). And comply with the local ethics board (Ethikkommission Heidelberg) as well as national laws regarding individual healing attempts. Patients are extensively informed by the treating physician about the nature of the therapy, the procedures, the risks and benefits. All patients give written informed consent before beginning with the procedure. Individual healing attempts need the approval for reimbursement by the patie...

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B., Silberstein, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Occipital+Nerve+stimulation+for+primary+headaches.">Occipital Nerve stimulation for primary headaches.</a> J Neurosurg Sci. 56 (4), 307-312 (2012).</li><li>Jakobs, M., Unterberg, A., Treede, R. D., Schuh-Hofer, S., Ahmadi, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subcutaneous+trigeminal+nerve+field+stimulation+for+refractory+trigeminal+pain:+a+cohort+analysis.">Subcutaneous trigeminal nerve field stimulation for refractory trigeminal pain: a cohort analysis.</a> Acta Neurochir. (Wien). 158 (9), 1767-1774 (2016).</li><li>Klein, J., Sandi-Kahun, S., Schackert, G., Juratli, T. 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With subcutaneous trigeminal nerve field stimulation (sTNFS), we present a surgical technique to perform minimally invasive neuromodulation for chronic refractory pain of the trigeminal nerve of different etiologies.
To reduce complications thorough disinfection of the entire surgical field is vital. Any unnecessary skin perforation can increase the risk of device infection with the consecutive loss of the system. Physicians should always pay attention to the implantation depth of the electrod...

The neurosurgical armamentarium to treat trigeminal pain is as large and diverse as the underlying etiologies. In cases of classical trigeminal neuralgia (TN) caused by arterial compression at the brainstem root entry zone of the trigeminal nerve microvascular decompression (MVD)1 is highly effective. Percutaneous destructive techniques at the Gasserian Ganglion (such as radiofrequency thermocoagulation, glycerol injection or balloon compression2) and stereotactic radiosurgery for trigeminal neuralgia3 can be applied in cases without neurovascular conflict or whenever there are contraindications for open microsurgery. However, all techniques are associated with certain recurrence rates of pain. Furthermore, the treatment itself bears risks for nerve damage resulting in neuropathic pain or even painful post-traumatic trigeminal neuropathy. AT last, trigeminal pain of central origins (e.g. post stroke pain) will not respond to MVD or destructive techniques at the Gasserian Ganglion but needs to be treated by neuromodulation such as deep brain stimulation (DBS) or motor cortex stimulation (MCS).
Neuromodulation is a term used for surgical techniques that appear to alter neural activity without causing irreversible tissue damage. Neuromodulative treatments are reversible, adaptable and usually work with intermittent or continuous application of electrical currents to parts of the peripheral or central nervous system. There are several certified (CE and/or FDA approved) treatments available to treat chronic and/or neuropathic pain of the trunk and the extremities such as epidural spinal cord stimulation (SCS), peripheral nerve field stimulation (PNFS) or dorsal root ganglion stimulation (DRG)4. However, currently there is no CE or FDA approved treatment available for chronic neuropathic facial and trigeminal pain.
Deep brain stimulation (DBS) and motor cortex stimulation (MCS) have been applied in multiple case series for patients with chronic facial pain of different origins5. However, both techniques present a high level of complexity and demand special physician expertise. There is a need for simple, cost efficient and effective neuromodulation for chronic trigeminal and facial pain when conservative treatment fails and destructive techniques want to be avoided.
Besides surgical approaches an array of non-invasive or temporary forms of neuromodulation is available to treat chronic pain (e.g. PENS: percutaneous electrical neurostimulation, TENS: transcutaneous electrical neurostimulation, TMS: transcranial magnetic stimulation).
Subcutaneous peripheral nerve field stimulation (sPNFS) is the least invasive form of neuromodulation6. One or more electrodes are placed in the subcutaneous tissue in the painful area. Continuous electrical stimulation is applied to create a pleasant paresthesia that covers the painful area. The exact mechanism of action is not known. However, despite all shortcomings the similar mechanisms like in the gate control theory &#8211; or variations of it &#8211; which postulates modulation of nociceptive input by inhibitory fibers is most often applied. Furthermore a local depolarization block of the peripheral nerve fibers with reduced excitability and changes in the micro environment regarding inflammatory proteins are discussed7.
As in most neuromodulation procedures a test trial with externalized electrodes connected to a pulse generator is performed to evaluate the effectiveness before a fully implantable pulse generator (IPG) is placed in the subcutaneous tissue and connected to the electrodes as the power source for the stimulation in case of therapeutic success. There is no general definition of a positive test trial however a reduction in pain of 50% or more on the visual analog scale (VAS) is most often regarded as a hallmark criterion. Furthermore, reduction in oral pain medication or increase in quality of life can be factors to favor implantation of a permanent system.
Peripheral nerve field stimulation is certified for the use in chronic low back pain8 and has been used for localized chronic pain syndromes (e.g. post-herniorrhaphy pain). It is also used as occipital nerve stimulation (ONS) to treat chronic migraine and cluster headaches9. Several non-randomized studies have shown the use of sPNFS in the trigeminal dermatomes for chronic and neuropathic intractable pain of different origins (classical TN, atypical TN, post-herpetic trigeminal neuropathy, MS associated trigeminal neuropathy, persistent idiopathic facial pain)10,11,12.
Subcutaneous trigeminal nerve field stimulation (sTNFS) is easy and fast to perform. Contrary to DBS or MCS, sTNFS can be performed as an outpatient procedure (if reimbursed). There is no risk of intracranial or epidural bleeding. Seizures do not occur. Trial stimulation is performed in an ambulatory setting so that the patient can assess the stimulation effect while performing his everyday routine rather than being bound to a hospital bed. No extensive intra- or preoperative imaging is necessary to determine the correct position of the electrodes. sTNFS can be considered as a therapeutic option to modulate pain perception and processing before applying a percutaneous destructive procedure or as a less invasive type of neuromodulation before thinking about MCS or DBS in patients with neuropathic or central pain.

<table border="0" cellpadding="0" cellspacing="0" width="1257">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">myStim Patient Programmer</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">97740</td>
			<td style="width:709px;">enables the patient to turn off and on stimulation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Prime Advanced</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">97702</td>
			<td>non-rechargeable IPG as powersource for stimulation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Restore Ultra</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">97712</td>
			<td>rechargeable IPG as powersource for stimulation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Charging System</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">97754</td>
			<td>used by the patient to recharge the Restore Ultra IPG</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">N&#39;Vision Programmer</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">8840</td>
			<td>used by the physician to program the IPG and define stimulation parameters</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">External Neurostimulator</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">37022</td>
			<td>external IPG as powersource for trial stimulation with externalized electrodes</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Advanced Screening Cable</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">355531</td>
			<td>connects externalized electrodes to the external neurostimulator during trial stimulation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Tunnelling Spear 60cm</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">3655-60</td>
			<td>used to subcutaneously tunnel the permanent electrodes to an infraclavicular pocket that houses the IPG</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Tunnelling Spear 38cm</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">3655-38</td>
			<td>used to subcutaneously tunnel the permanent electrodes to an infraclavicular pocket that houses the IPG</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Tuhoy Cannula</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">3550-32</td>
			<td>14 gauge Epidural Tuhoy cannula (length 9cm) to subcutaneously implant the electrodes</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">InjexFixation Device</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">97791 / 97792</td>
			<td>used to fixate the electrodes on the skin or on the muscle fascia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Octad Compact</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">3878-60</td>
			<td>permanent electrode (length 60cm) implanted in the subcutaneous tissue with 8 contacts</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Vectris Trial Lead</td>
			<td style="width:213px;">Medtronic</td>
			<td style="width:119px;">977D260</td>
			<td>externalized electrode (length 60cm) used during the stimulation trial</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Ethilon*II 3-0</td>
			<td style="width:213px;">Ethicon</td>
			<td style="width:119px;">EH7933H</td>
			<td>non-absorbable suture for skin closure</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Seide 2-0</td>
			<td style="width:213px;">Resorba</td>
			<td style="width:119px;">40221</td>
			<td>non-absorbable silk suture to fixate electrodes and IPG</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Resolon DS21</td>
			<td style="width:213px;">Resorba</td>
			<td style="width:119px;">881413</td>
			<td>absorbable suture for subcutaneous wound closure</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Feather disposable scalpel</td>
			<td style="width:213px;">Feather</td>
			<td style="width:119px;">5205052</td>
			<td>single use scalpel for skin incision and suture cutting</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Scandicain 1%</td>
			<td style="width:213px;">Astra Zeneca</td>
			<td style="width:119px;">23186</td>
			<td>1% Mepivacain solution for local anesthesia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Cosmopor E steril 10x6</td>
			<td style="width:213px;">Hartmann</td>
			<td style="width:119px;">900871</td>
			<td>Sterile draping for IPG wound</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Cosmopor E steril 7,2x5</td>
			<td style="width:213px;">Hartmann</td>
			<td style="width:119px;">900870</td>
			<td>Sterile draping for skin punctures and small incisions</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Foliodrape Comfort 50x50</td>
			<td style="width:213px;">Hartmann</td>
			<td style="width:119px;">252302</td>
			<td>Sterile draping for the surgical field</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Cephazolin</td>
			<td style="width:213px;">Fresenius</td>
			<td style="width:119px;">6062403.00.00</td>
			<td>Single shot perioperative antibiotic</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Kepinol forte 800mg/160mg</td>
			<td style="width:213px;">Dr. R. Pfleger Chemische Fabrik</td>
			<td style="width:119px;">2485177</td>
			<td>Postoperative prophylactic oral antibiotic</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Poly-Alcohol</td>
			<td style="width:213px;">Antiseptica</td>
			<td style="width:119px;">UN1219</td>
			<td>Coloured skin disinfectant used during the permanent implantation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Cutasept F</td>
			<td style="width:213px;">Bode</td>
			<td style="width:119px;">976800</td>
			<td>Un-Coloured skin disinfectant used during the trial implantation</td>
		</tr>
	</tbody>
</table>

subcutaneous trigeminal nerve field stimulation for refractory facial pain

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. Neuromodulation techniques for chronic facial pain include deep brain stimulation and motor cortex stimulation, which are complex to perform. Subcutaneous nerve field stimulation is certified for chronic back pain and is the least invasive form of neuromodulation. We applied this technique to treat chronic and neuropathic trigeminal pain as an individual therapy concept. First, trial stimulation is performed. Subcutaneous leads are placed in the painful trigeminal dermatome under local anesthesia. The leads are connected to an external neurostimulator that applies constant stimulation. Patients undergo a 12 day outpatient trial to assess the effect of the stimulation. Electrodes are removed after the trial. If the patient reports pain reduction of at least 50% in intensity and/or attack frequency, a reduction in medication or increase in quality of life, permanent implantation is scheduled. New electrodes are implanted under general anesthesia and are subcutaneously tunneled to an infraclavicular internal pulse generator. Patients are able to turn stimulation on and off and to increase or decrease the stimulation amplitude as needed.
This technique represents a minimal invasive alternative to other more invasive means of neuromodulation for trigeminal pain such as motor cortex stimulation or deep brain stimulation.

As subcutaneous trigeminal nerve field stimulation (sTNFS) is not a standard treatment and the number of patients that can potentially benefit from it is rather small compared to other diseases, there are only smaller case series that present results of sTNFS. In one series, 10 patients underwent test stimulation for sTNFS. Eight of the patients responded to the therapy and received permanent implantation of electrodes and an IPG11. The patients suffered from trige...

Watch this Scientific Journal Video about Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain at JoVE.com

Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain

Treating chronic or neuropathic facial pain can be challenging when medical or standard treatment fails. Subcutaneous nerve field stimulation is the least invasive form of neuromodulation and is used for chronic back pain. We applied this technology to treat chronic and neuropathic trigeminal facial pain.

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. ...

The overall goal of this surgical intervention is to treat patients with chronic therapy-resistant and neuropathic trigeminal pain using minimally invasive subcutaneous nerve field stimulation as a method of neuromodulation. This method can help treat patients with therapy-resistant chronic trigeminal pain such as trigeminal neuralgia or post-therapeutic trigeminal neuropathy who have failed conservative and standard surgical treatment. The main advantage of this technique is that it is minimally invasive, does not destroy any nerve tissue, and its success can be tested in a period of trial stimulation before undergoing permanent implantation.We offer this treatment as an alternative to destructive techniques such as Radiofrequency Thermocoagulation or Gamma Knife Radiosurgery. After a patient has carried out a 12-day stimulation trial, according to the text protocol, turn the anesthetized patient's head to the side contralateral to the pain. Then, place a pillow under the ipsilateral shoulder to expose the clavicle.Shave the area around the ear on the painful side of the face. Then remove any loose hair. If necessary, tape away the surrounding hair to prevent it from moving into the surgical field.Next, thoroughly disinfect the surgical field from the facial area around the ear and down to the clavicle area. From the X-rays of the out-patient appointment, use a sterile surgical pen to mark the desired position of the permanent electrodes in the marks of the previous skin punctures for guidance. For the first trigeminal branch, choose a position on the lateral side of the forehead at which to puncture the skin, roughly 10 centimeters lateral and one centimeter above the medial border of the eyebrow.For the second trigeminal branch, choose a position that is located roughly one centimeter anterior to the tragus. Do not perform a skin puncture two centimeters or more anterior to the tragus to spare facial nerve fibers from injury. For the third trigeminal branch, choose a position that is located roughly one centimeter anterior and four centimeters below the tragus.Correct planning of electrode insertion is crucial to the success of this technique as the parasthesia provoked by the stimulation should cover the entire painful area. Use a 14-gauge Tuohy needle to perform a skin puncture at a previously marked position. As the subcutaneous tissue of the facial area is thinner than on other body parts, make sure to stay half a centimeter below the skin surface to prevent skin perforation or direct muscle stimulation.Make a one centimeter-long vertical incision in the supra-auricular area. And form a small subcutaneous pocket. Take the stylets from the Tuohy cannulas and subcutaneously tunnel them from the site of the skin puncture to the supra-auricular incision.Insert another Tuohy cannula to subcutaneously tunnel from the supra-auricular incision to the site of the skin puncture. And then insert the electrodes into the Tuohy cannula with the contacts located in the painful area. Remove the Tuohy cannulas and the electrode stylets.And insert the distal end of the electrode into the cannula. Remove the Tuohy cannula while using forceps to keep the electrode in place. Then use a 3-0 non-absorbable silk suture to fix the electrode to the muscle fascia to prevent electrode dislocation.Next, perform a six centimeter long infraclavicular incision and manually form a subcutaneous pocket to house the IPG. Use bipolar electrical forceps to coagulate any bleeding vessels. Insert a tunneling spear into the infraclavicular incision and subcutaneously tunnel behind the ear towards the supra-auricular incision.Make a small retroauricular incision for the spear to exit the skin. Then, tunnel with a second spear from the supra-auricular to the retroauricular incision. Remove the spear stylets.And insert the electrodes until the electrodes are buried in the subcutaneous tissue without any loops or kinks. After tunneling the electrodes to the retroauricular incision, tunnel them from here to the infraclavicular incision. Then remove the spear by pulling it out of the infraclavicular incision while using forceps to keep the electrodes in place.Connect the electrodes to the IPG. And use torque screws to secure them. Use a non-absorbable 3-0 silk suture to suture the IPG to the pectoralis muscle fascia to prevent IPG dislocation.Perform skin closure with absorbable 3-0 subcutaneous sutures and non-absorbable 3-0 cutaneous sutures in the facial area. And absorbable 3-0 intracutaneous sutures at the site of the IPG. Then disinfect all wounds.Clean the surgical field with saline. And apply sterile draping. Carry out post-operative care according to the text protocol.In one case series, 10 patients who suffered from pain from the conditions listed in this table underwent test stimulation for subcutaneous trigeminal nerve field stimulation, or sTNFS, and received permanent implantation of electrodes and an IPG. Following an 11-month follow-up, eight of the 10 patients responded to the therapy with pain reduced from 9.3 to 0.75 on the Visual Analog Scale. In another recently published series, eight patients were tested with sTNFS.After a mean follow-up of 15.2 months, six of the eight patients proceeded to permanent implantation. And according the VAS, pain was reduced from 8.5 to 1.4 points. The series is also the first to describe a 73%reduction in the mean number of painful daily attacks.The chart shown here was all patients with permanent implantations treated with sTNFS. A mean reduction of 6.8 VAS points and the mean reduction of 12.2 in the number of daily attacks was achieved. Trial electrode placement takes roughly 15 minutes.The surgery for permanent implantation can be performed within one hour and patients can be discharged on the next day. Subcutaneous trigeminal nerve field stimulation can provide a sustained therapeutic effect on both pain intensity and frequency of painful attacks. The amount of pain medication and its side effects can then be reduced.After watching this video, you should have a good understanding of how to perform trial electrode placement and permanent implantation surgery for subcutaneous trigeminal nerve field stimulation.

subcutaneous-trigeminal-nerve-field-stimulation-for-refractory-facial

Research

JoVE Journal

Medicine

Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats

Chronic neuropathic pain, resulting from damage to the central or peripheral nervous system, is a prevalent and debilitating condition, affecting 7-18% of the population1,2. Symptoms include spontaneous (tingling, burning, electric-shock like) pain, dysaesthesia, paraesthesia, allodynia (pain resulting from normally non-painful stimuli) and hyperalgesia (an increased response to painful stimuli). The sensory symptoms are co-morbid with behavioural disabilities, such as insomnia and depression. To study chronic neuropathic pain several animal models mimicking peripheral nerve injury have been developed, one of the most widely used is Bennett and Xie's (1988) unilateral sciatic nerve chronic constriction injury (CCI)3 (Figure 1). Here we present a method for performing CCI and testing pain hypersensitivity.
CCI is performed under anaesthesia, with the sciatic nerve on one side exposed by making a skin incision, and cutting through the connective tissue between the gluteus superficialis and biceps femoris muscles. Four chromic gut ligatures are tied loosely around the sciatic nerve at 1 mm intervals, to just occlude but not arrest epineural blood flow. The wound is closed with sutures in the muscle and staples in the skin. The animal is then allowed to recover from surgery for 24 hrs before pain hypersensitivity testing begins.
For behavioural testing, rats are placed into the testing apparatus and are allowed to habituate to the testing procedure. The area tested is the mid-plantar surface of the hindpaw (Figure 2), which falls within the sciatic nerve distribution. Mechanical withdrawal threshold is assessed by mechanically stimulating both injured and uninjured hindpaws using an electronic dynamic plantar von Frey aesthesiometer or manual von Frey hairs4. The mechanical withdrawal threshold is the maximum pressure exerted (in grams) that triggers paw withdrawal. For measurement of thermal withdrawal latency, first described by Hargreaves et al (1988), the hindpaw is exposed to a beam of radiant heat through a transparent glass surface using a plantar analgesia meter5,6. The withdrawal latency to the heat stimulus is recorded as the time for paw withdrawal in both injured and uninjured hindpaws. Following CCI, mechanical withdrawal threshold, as well as thermal withdrawal latency in the injured paw are both significantly reduced, compared to baseline measurements and the uninjured paw (Figure 3). The CCI model of peripheral nerve injury combined with pain hypersensitivity testing provides a model system to investigate the effectiveness of potential therapeutic agents to modify chronic neuropathic pain. In our laboratory, we utilise CCI alongside thermal and mechanical sensitivity of the hindpaws to investigate the role of neuro-immune interactions in the pathogenesis and treatment of neuropathic pain.

Due to the simplicity of surgery and the robust behavioural outcome, chronic constriction of the sciatic nerve is one of the pre-eminent animal models of neuropathic pain. Within 24 hrs following surgery, pain hypersensitivity is established and can be quantitatively measured using a von Frey aesthesiometer (mechanical test) and plantar analgesia meter (thermal test).

Chronic neuropathic pain, resulting from damage to the central or peripheral nervous system, is a prevalent and debilitating condition, affecting 7-18% of ...

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. It has been extensively used in various clinical settings. Based upon recent discoveries related to the systemic effects of voluntary breathing and intrinsic physiological interactions among systems during voluntary breathing, a new EStim protocol, Breathing-controlled Electrical Stimulation (BreEStim), has been developed to augment the effects of electrical stimulation. In BreEStim, a single-pulse electrical stimulus is triggered and delivered to the target area when the airflow rate of an isolated voluntary inspiration reaches the threshold. BreEStim integrates intrinsic physiological interactions that are activated during voluntary breathing and has demonstrated excellent clinical efficacy. Two representative applications of BreEStim are reported with detailed protocols: management of post-stroke finger flexor spasticity and neuropathic pain in spinal cord injury.

Breathing-controlled Electrical Stimulation BreEStim for Management of Neuropathic Pain and Spasticity

The purpose is to present a new method, breathing-control electrical stimulation (BreEStim) for management of neuropathic pain and spasticity.

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. ...

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in injured sensory neurons and along the entire nociceptive pathway within the central nervous system. It is usually chronic and challenging to treat. In order to study neuropathic pain and its treatments, different models have been developed in rodents. These models derive from known etiologies, thus reproducing peripheral nerve injuries, central injuries, and metabolic-, infectious- or chemotherapy-related neuropathies. Murine models of peripheral nerve injury often target the sciatic nerve which is easy to access and allows nociceptive tests on the hind paw. These models rely on a compression and/or a section. Here, the detailed surgery procedure for the &#34;cuff model&#34; of neuropathic pain in mice is described. In this model, a cuff of PE-20 polyethylene tubing of standardized length (2 mm) is unilaterally implanted around the main branch of the sciatic nerve. It induces a long-lasting mechanical allodynia, i.e., a nociceptive response to a normally non-nociceptive stimulus that can be evaluated by using von Frey filaments. Besides the detailed surgery and testing procedures, the interest of this model for the study of neuropathic pain mechanism, for the study of neuropathic pain sensory and anxiodepressive aspects, and for the study of neuropathic pain treatments are also discussed.

Neuropathic pain is a consequence of a lesion or disease affecting the somatosensory system. The &#8220;cuff model&#8221; of neuropathic pain in mice consists of the implantation of a polyethylene cuff around the main branch of the sciatic nerve. Mechanical allodynia is tested using von Frey filaments.

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in ...

Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury

The goal of this surgical protocol is to expose the facial nerve, which innervates the facial musculature, at its exit from the stylomastoid foramen and either cut or crush it to induce peripheral nerve injury. Advantages of this surgery are its simplicity, high reproducibility, and the lack of effect on vital functions or mobility from the subsequent facial paralysis, thus resulting in a relatively mild surgical outcome compared to other nerve injury models. A major advantage of using a cranial nerve injury model is that the motoneurons reside in a relatively homogenous population in the facial motor nucleus in the pons, simplifying the study of the motoneuron cell bodies. Because of the symmetrical nature of facial nerve innervation and the lack of crosstalk between the facial motor nuclei, the operation can be performed unilaterally with the unaxotomized side serving as a paired internal control. A variety of analyses can be performed postoperatively to assess the physiologic response, details of which are beyond the scope of this article. For example, recovery of muscle function can serve as a behavioral marker for reinnervation, or the motoneurons can be quantified to measure cell survival. Additionally, the motoneurons can be accurately captured using laser microdissection for molecular analysis. Because the facial nerve axotomy is minimally invasive and well tolerated, it can be utilized on a wide variety of genetically modified mice. Also, this surgery model can be used to analyze the effectiveness of peripheral nerve injury treatments. Facial nerve injury provides a means for investigating not only motoneurons, but also the responses of the central and peripheral glial microenvironment, immune system, and target musculature. The facial nerve injury model is a widely accepted peripheral nerve injury model that serves as a powerful tool for studying nerve injury and regeneration.

We present a surgical protocol detailing how to perform a cut or crush axotomy on the facial nerve in the mouse. The facial nerve axotomy can be employed to study the physiological response to nerve injury and test therapeutic techniques.

The goal of this surgical protocol is to expose the facial nerve, which innervates the facial musculature, at its exit from the stylomastoid foramen and ...

Chronic Constriction Injury of the Rat's Infraorbital Nerve (IoN-CCI) to Study Trigeminal Neuropathic Pain

Animal models are important tools to study the pathophysiology and pharmacology of neuropathic pain. This manuscript describes the surgical and behavioral procedures to study trigeminal neuropathic pain in rats. To meet the specificity of trigeminal neuropathic pain syndromes, the infraorbital nerve (IoN) is subjected to a chronic constriction injury (CCI) by loosely ligating the nerve. An intra-orbital approach is presented here to expose and ligate the IoN in the orbital cavity. After IoN ligation, rats exhibit changes in spontaneous behavior and in response to von Frey hair stimulation that are indicative of persistent pain and mechanical allodynia. Two phases can be defined in the development of the behavioral changes. During the first week following IoN-CCI (phase 1), rats show an increased and asymmetric face grooming activity, i.e., with face wash strokes primarily directed to the nerve-injured IoN territory. A distinction is made between face grooming behavior that is part of a more general body grooming behavior, which remains largely unaffected by IoN-CCI, and face grooming that is neither preceded nor followed by body grooming, which is significantly increased after IoN-CCI. During this period, responsiveness to mechanical stimulation of the IoN territory is reduced. This hyporesponsiveness is abruptly replaced by an extreme hyperresponsiveness whereby even very weak stimulus intensities provoke nocifensive behavior (phase 2). The phenomenological similarities between these behavioral alterations and reported signs of facial pain (i.e., responses to noxious stimulation of the face) suggest the presence of dysesthesia/paresthesia and mechanical allodynia in the ligated IoN territory.

Chronic Constriction Injury of the Rat's Infraorbital Nerve IoN-CCI to Study Trigeminal Neuropathic Pain

This manuscript describes a rodent model to study trigeminal neuropathic pain. The methods described include surgical procedures to perform a chronic constriction injury of the rat&#8217;s infraorbital nerve and the post-surgical behavioral tests to measure the changes in spontaneous and evoked behavior that are indicative of persistent pain and allodynia.

Animal models are important tools to study the pathophysiology and pharmacology of neuropathic pain. This manuscript describes the surgical and behavioral ...

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area.

This protocol describes a procedure to track the evolution of mesial network measures in temporal lobe epilepsy (TLE) patients. It is based on the combination of intracranial recordings with a novel numerical technique for data analysis. Specifically, we present a protocol for network analyses of foramen ovale recordings.

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control ...

MRI-guided Focused Ultrasound Thalamotomy for Patients with Medically-refractory Essential Tremor

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ET can have a significant impact on quality of life, mood, functional activities, and socialization. Patients suffering from ET not sufficiently treated with first line medications may be eligible for alternative strategies such as deep brain stimulation, radiofrequency ablation, and MRI guided focused ultrasound (MRgFUS). High-intensity MRgFUS is an emerging modality to treat ET, its attraction for patients being that it is noninvasive and associated with short recovery time, as patients are home the day after treatment. While MRgFUS centers are still limited, it will become important for clinicians to consider MRgFUS as a treatment alternative, particularly in the case of a patient for whom open surgery is contraindicated. This article outlines the steps of patient selection, equipment setup, sonication, and post-treatment follow-up, as well as critical steps to be aware of when performing a MRgFUS procedure.

High-intensity MRI guided focused ultrasound is an emerging noninvasive technique to precisely ablate brain tissue. It has been shown to be safe and effective in treating medically-refractory essential tremor. This article describes the protocol for thalamotomy from patient selection to equipment setup to post-treatment follow-up.

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ...

Cavernous Nerve Stimulation and Recording of Intracavernous Pressure in a Rat

The stimulation of the cavernous nerve (CN) and measurement of intracavernous pressure (ICP) have been used extensively to test and evaluate therapies for erectile dysfunction. However, the methods used vary between laboratories, and pitfalls still exist. The goal of this study was to describe a surgical technique that would provide a reliable and reproducible model. By exposing the ischiocavernosus muscle at its point of insertion on the ischial tuberosity, the penile crus could be cannulated with minimal dissection and injury to the structures involved in erectile function. Repeated stimulation of the CN, without the need for lifting and drying, was achieved by using a 125 &#181;m bipolar silver electrode and biocompatible silicon glue to isolate the electrode-nerve complex. This method prevents neuropraxia by reducing stretching and drying the nerve and provides complete isolation of the nerve, negating electrical leakage and preventing stimulation of alternative pathways.

This study describes a simplified surgical procedure and technique for performing cavernous nerve stimulation with the isolation of the nerve-electrode complex using silicone glue and intracavernous pressure measurement.

The stimulation of the cavernous nerve (CN) and measurement of intracavernous pressure (ICP) have been used extensively to test and evaluate therapies for ...

Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression (TRD). VNS exhibits antidepressive and stabilizing effects. This method is particularly useful as a long-term treatment, in which up to two-thirds of patients respond. The vagus nerve stimulator is positioned on the left vagus nerve during a surgical procedure and is activated telemetrically by a wand connected to a handheld computerized device. The treating physician can perform various adjustments of the vagus nerve stimulator during in-office visits (e.g., by modifying stimulation intensity or stimulation frequency) to achieve maximum therapeutic effects with low side effects. Set-up of the device usually takes several months. Typical side effects include wound infection, temporary salivation, coughing, paralysis of the vocal cords, bradycardia, or even asystole. The patient can stop the VNS by placing a magnet over the generator. The current protocol describes delivery of the specific stimulation tool and methods for adjusting the tuning parameters to achieve the best remission rates in patients with TRD.

Vagus nerve stimulation (VNS) has been shown to be effective as an adjunct treatment for treatment-resistant depression (TRD). VNS leads to antidepressive and antisuicidal effects and quality of life improvements. This protocol offers a step-by-step guide to managing and adjusting a vagus nerve stimulator for efficient treatment of TRD.

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression ...

FSN Therapy for Knee Osteoarthritis Pain Management

Fu's Subcutaneous Needling for Knee Osteoarthritis Pain

Fu's subcutaneous needling (FSN) is a new acupuncture and dry needling technique based on traditional Chinese medicine. It rapidly produces long-lasting effects in soft tissue injuries, particularly in painful musculoskeletal conditions, by providing stimulation primarily in the subcutaneous area. Osteoarthritis (OA) is the most common joint disease in adults worldwide and is often accompanied by a painful syndrome of structural changes in the peripheral joints of the knee. However, the etiology of OA pain is not fully understood, though myofascial trigger points (MTrPs) are commonly found in the lower limb muscles (so-called "tightened muscles") of patients with knee OA. 
FSN has been used in many fields for the treatment of acute pain problems and can relieve muscle contraction from MTrPs, thereby improving the local circulation. This study recruited patients with pain from knee OA into an FSN group or a transcutaneous electrical nerve stimulation (TENS) group with three treatment sessions and a follow-up over the course of 2 weeks. The results showed that FSN was effective in treating soft tissue pain around the knee with OA. This study aimed to establish and visualize three key technical indicators during FSN therapy, including the FSN needle insertion point and layer; the frequency and duration of the swaying movement; and the manipulation of the reperfusion approach. These findings have great potential for future applications in myofascial pain treatment, especially for pain management. Following this protocol could enhance FSN skills.

Author Spotlight: Fu's Subcutaneous Needling for Knee Osteoarthritis Pain  

We present a protocol for using Fu's subcutaneous needling for knee osteoarthritis pain, which combines swaying movement and reperfusion approach techniques. This protocol has great potential for future applications in myofascial pain treatment and could enhance Fu's subcutaneous needling (FSN) manipulation skills.

Fu's subcutaneous needling (FSN) is a new acupuncture and dry needling technique based on traditional Chinese medicine. It rapidly produces long-lasting ...