Dynamic Quantitative Sensory Testing to Characterize Central Pain Processing

Central facilitation and modulation of incoming nociceptive signals play an important role in the perception of pain. Disruption in central pain ...

Stanford University School of Medicine

To determine whether the characteristics of disease due to Toxoplasma gondii (toxoplasmosis) are dependent on the infecting strain, we have developed an enzyme-linked immunosorbent assay for typing strains that uses infection serum reacted against polymorphic peptides derived from Toxoplasma antigens SAG2A, GRA3, GRA6, and GRA7. Pilot studies with infected mice established the validity of the approach, which was then tested with human serum. In 8 patients who had Sabin-Feldman dye test titers >64 and for whom the infecting strain type was known, the peptides correctly distinguished type II from non-type II infections. ELISA analysis of a second group of 10 infected pregnant women from whom the parasite strain had not been isolated gave a clear prediction of the strain type causing infection. This method should allow statistically significant data to be obtained about whether different strain types cause disease with different characteristics.

Serotyping of Toxoplasma gondii infections in humans using synthetic peptides.

Recent efforts to use fMRI to investigate the effects of acupuncture needle manipulation on the brain have yielded discrepant results. This study was designed to test the reliability of fMRI signal changes evoked by acupuncture stimulation. Six subjects participated in six identical scanning sessions consisting of four functional scans, one for each of the four conditions: electroacupuncture stimulation (2 Hz) at GB 37, UB 60, non-acupoint (NP), and a control task of the finger tapping. In the group analysis across all subjects and sessions, both the average ratings on a Subjective Acupuncture Sensation Scale and the average fMRI signal changes (increases and decreases) were similar for GB37, UB 60, and NP. Visual inspection of the activation maps from individual sessions and ICC analysis revealed that fMRI signal changes evoked by electroacupuncture stimulation were significantly more variable than those from the control finger-tapping task. The relatively large variability across different sessions within the same subject suggests multiple sessions should be used to accurately capture the activation patterns evoked by acupuncture stimulation at a particular point for a specific subject.

Test-retest study of fMRI signal change evoked by electroacupuncture stimulation.

The concept that specific acupuncture points have salubrious effects on distant target organ systems is a salient feature of Traditional Chinese Medicine (TCM). In this study, we used a multiple-session experiment to test whether electroacupuncture stimulation at two TCM vision-related acupoints, UB 60 and GB 37, located on the leg, could produce fMRI signal changes in the occipital regions of the brain, and the specificity of this effect when compared with stimulation at an adjacent non-acupoint (NAP). Six normal, acupuncture naive subjects completed the study. Each subject participated in six identical scanning sessions. Voxelwise group analysis showed that electroacupuncture stimulation at both vision-related acupoints and the NAP produced modest, comparable fMRI signal decreases in the occipital cortex, including the bilateral cuneus, calcarine fissure and surrounding areas, lingual gyrus, and lateral occipital gyrus. Further analysis of fMRI signal changes in occipital cortex showed no significant difference among the three points, UB 60, GB 37, and NAP. Our results thus do not support the view that acupuncture stimulation at vision-related acupoints induces specific fMRI blood oxygen level dependent (BOLD) signal changes in the occipital cortex. We speculate that cross modal inhibition, produced by needling-evoked somatosensory stimulation, may account for our finding of BOLD signal decreases in the occipital cortex. Given the complexity of acupuncture systems and brain activity, additional work is required to determine whether functional neuroanatomical correlates of acupoint specificity can be validated by means of brain imaging tools.

Functional neuroanatomical investigation of vision-related acupuncture point specificity--a multisession fMRI study.

Temporal summation (TS) refers to the increased perception of pain with repetitive noxious stimuli. It is a behavioral correlate of wind-up, the spinal facilitation of recurring C-fiber stimulation. In order to utilize TS in clinical pain research, it is important to characterize TS in a wide range of individuals and to establish its test-retest reliability. Building on a fixed-parameter protocol, we developed an individually adjusted protocol to broadly capture thermally generated TS. We then examined the test-retest reliability of TS within-day (intertrial intervals ranging from 2 to 30 minutes) and between-days (intersession interval of 7 days). We generated TS-like effects in 19 of the 21 participants. Strong correlations were observed across all trials over both days (intraclass correlation [ICC] [A, 10] = .97, 95% confidence level [CL] = .94-.99) and across the initial trials between days (ICC [A, 1] = .83, 95% CL = .58-.93). Repeated measures mixed-effects modeling demonstrated no significant within-day variation and only a small (5 out of 100 points) between-day variation. Finally, a Bland-Altman analysis suggested that TS is reliable across the range of observed scores. Without intervention, thermally-generated TS is generally stable within day and between days.

Test-retest reliability of thermal temporal summation using an individualized protocol.

Approximately 10% of patients following a variety of surgeries develop chronic postsurgical pain. Reducing chronic postoperative pain is especially important to reconstructive surgeons because common operations such as breast and limb reconstruction have even higher risk for developing chronic postsurgical pain. Animal studies of posttraumatic nerve injury pain demonstrate that there is a critical time frame before and immediately after nerve injury in which specific interventions can reduce the incidence and intensity of chronic neuropathic pain behaviors-so called "preventative analgesia." In animal models, perineural local anesthetic, systemic intravenous local anesthetic, perineural clonidine, systemic gabapentin, systemic tricyclic antidepressants, and minocycline have each been shown to reduce pain behaviors days to weeks after treatment. The translation of this work to humans also suggests that brief perioperative interventions may protect patients from developing new chronic postsurgical pain. Recent clinical trial data show that there is an opportunity during the perioperative period to dramatically reduce the incidence and severity of chronic postsurgical pain. The surgeon, working with the anesthesiologist, has the ability to modify both early and chronic postoperative pain by implementing an evidence-based preventative analgesia plan.

Perioperative interventions to reduce chronic postsurgical pain.

We discuss the emerging translational tools for the study of acupuncture analgesia with a focus on psychophysical methods. The gap between animal mechanistic studies and human clinical trials of acupuncture analgesia calls for effective translational tools that bridge neurophysiological data with meaningful clinical outcomes. Temporal summation (TS) and conditioned pain modulation (CPM) are two promising tools yet to be widely utilized. These psychophysical measures capture the state of the ascending facilitation and the descending inhibition of nociceptive transmission, respectively. We review the basic concepts and current methodologies underlying these measures in clinical pain research, and illustrate their application to research on acupuncture analgesia. Finally, we highlight the strengths and limitations of these research methods and make recommendations on future directions. The appropriate addition of TS and CPM to our current research armamentarium will facilitate our efforts to elucidate the central analgesic mechanisms of acupuncture in clinical populations.

Understanding central mechanisms of acupuncture analgesia using dynamic quantitative sensory testing: a review.

Conditioned pain modulation (CPM) is an experimental approach for probing endogenous analgesia by which one painful stimulus (the conditioning stimulus) may inhibit the perceived pain of a subsequent stimulus (the test stimulus). Animal studies suggest that CPM is mediated by a spino-bulbo-spinal loop using objective measures such as neuronal firing. In humans, pain ratings are often used as the end point. Because pain self-reports are subject to cognitive influences, we tested whether cognitive factors would impact on CPM results in healthy humans.

Conditioned pain modulation is minimally influenced by cognitive evaluation or imagery of the conditioning stimulus.

In the field of acupuncture research there is an implicit yet unexplored assumption that the evidence on manual and electrical stimulation techniques, derived from basic science studies, clinical trials, systematic reviews, and meta-analyses, is generally interchangeable. Such interchangeability would justify a bidirectional approach to acupuncture research, where basic science studies and clinical trials each inform the other. This article examines the validity of this fundamental assumption by critically reviewing the literature and comparing manual to electrical acupuncture in basic science studies, clinical trials, and meta-analyses. The evidence from this study does not support the assumption that these techniques are interchangeable. This article also identifies endemic methodologic limitations that have impaired progress in the field. For example, basic science studies have not matched the frequency and duration of manual needle stimulation to the frequency and duration of electrical stimulation. Further, most clinical trials purporting to compare the two types of stimulation have instead tested electroacupuncture as an adjunct to manual acupuncture. The current findings reveal fundamental gaps in the understanding of the mechanisms and relative effectiveness of manual versus electrical acupuncture. Finally, future research directions are suggested to better differentiate electrical from manual simulation, and implications for clinical practice are discussed.

Manual and electrical needle stimulation in acupuncture research: pitfalls and challenges of heterogeneity.

Electroacupuncture in treating residual insomnia associated with depression: lessons learned.

Research into acupuncture has had ripple effects beyond the field of acupuncture. This paper identifies five exemplars to illustrate that there is tangible evidence of the way insights gleaned from acupuncture research have informed biomedical research, practice, or policy. The first exemplar documents how early research into acupuncture analgesia has expanded into neuroimaging research, broadening physiologic understanding and treatment of chronic pain. The second describes how the acupuncture needle has become a tool to enhance biomedical knowledge of connective tissue. The third exemplar, which illustrates use of a modified acupuncture needle as a sham device, focuses on emergent understanding of placebo effects and, in turn, on insights into therapeutic encounters in treatments unrelated to acupuncture. The fourth exemplar documents that two medical devices now in widespread use were inspired by acupuncture: transcutaneous electrical nerve stimulators for pain control and antinausea wrist bands. The final exemplar describes how pragmatic clinical trial designs applied in acupuncture research have informed current general interest in comparative effectiveness research. In conclusion, these exemplars of unanticipated outcomes of acupuncture research comprise an additional rationale for continued support of basic and clinical research evaluating acupuncture and other under-researched therapies.

Jiang-Ti Kong

Anesthesiology,
Perioperative and Pain Medicine,
Anesthesiology, Perioperative and Pain Medicine

Stanford University School of Medicine

Dynamic Quantitative Sensory Testing to Characterize Central Pain Processing

Jiang-Ti Kong

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Anesthesiology,Perioperative and Pain Medicine,Anesthesiology, Perioperative and Pain Medicine

Stanford University School of Medicine

Dynamic Quantitative Sensory Testing to Characterize Central Pain Processing

Anesthesiology,
Perioperative and Pain Medicine,
Anesthesiology, Perioperative and Pain Medicine