Name: chronic constriction of the sciatic nerve and pain hypersensitivity testing in rats
Uploaded: 2012-03-13T12:00:00
Description: Watch this Scientific Journal Video about Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats at JoVE.com

The authors would like to acknowledge the original description of the CCI model by Bennett and Xie (1988). 
This work was supported partially by grants from the National Health and Medical Research Council of Australia (ID # 568637) and the NSW Office for Science and Medical Research to GMT.

1. Sciatic Nerve Chronic Constriction
Aseptic techniques should be used for the surgical procedure. Disinfect the surgical work surface with 70% ethanol and prepare in advance sterile instruments (e.g., fine scissors, forceps, and retractor), gauzes, staples and swabs by autoclaving. For multiple surgeries, clean and resterilise instruments with 70% ethanol or a dry bead steriliser between rats. A surgical mask, hair bonnet and sterile gloves should be worn.
For const...

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CCI is a widely used peripheral nerve injury model of chronic neuropathic pain. It is relatively simple to perform, and produces robust and stable pain hypersensitivity for at least one month after injury. Following CCI, rats exhibit abnormal posture of the injured hindpaw (toes held together and plantar-flexed and paw everted), as well as repeated shaking, guarding and licking of the injured hindpaw suggesting the presence of spontaneous pain9. In addition to sensory dysfunction, several investigators have sh...

<table border="1">
<tbody>
 <tr>
 <td>Name of the reagent/equipment</td>
 <td>Company</td>
 <td>Catalogue number</td>
 <td>Comments </td>
 </tr>
 <tr>
 <td>Chromic gut</td>
 <td>Ethicon</td>
 <td>G-211</td>
 <td>4-0 thickness</td>
 </tr>
 <tr>
 <td>Isoflurane</td>
 <td>Delvet Pty. Ltd., Seven Hills, NSW</td>
 <td>n/a</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Mersilk</td>
 <td>Ethicon</td>
 <td>W-580</td>
 <td>5-0 thickness</td>
 </tr>
 <tr>
 <td>Autoclip</td>
 <td>Becton Dickinson</td>
 <td>427631 </td>
 <td>9 mm stainless steel</td>
 </tr>
 <tr>
 <td>Riodine</td>
 <td>Orion</td>
 <td>R1000802F</td>
 <td>1% w/v iodine</td>
 </tr>
 <tr>
 <td>Thermal plantar analgesia instrument</td>
 <td>Ugo Basile</td>
 <td>37370</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Dynamic plantar aesthesiometer </td>
 <td>Ugo Basile</td>
 <td>37400</td>
 <td>&nbsp;</td>
 </tr>
 </tbody>
</table>

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.

Watch this Scientific Journal Video about Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats at JoVE.com

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

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 ...

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