Reference Values of Conditioned Pain Modulation

BACKGROUND AND AIMS: Endogenous pain modulation can be studied in humans by conditioned pain modulation (CPM): pain induced by a test stimulus is attenuated by a distantly applied noxious conditioning stimulus. The detection of impaired CPM in individual patients is of potential importance to understand the pathophysiology and predict outcomes. However, it requires the availability of reference values. // METHODS: We determined reference values of CPM in 146 pain-free subjects. Pressure and electrical stimulation were the test stimuli. For electrical stimuli, we recorded both pain threshold and threshold for the nociceptive withdrawal reflex. Cold pressor test was the conditioning stimulus. The 5th, 10th and 25th percentiles for the three tests were computed by quantile regression analyses. // RESULTS: The average thresholds increased after the conditioning stimulus for all three tests. However, a subset of subjects displayed a decrease in thresholds during the conditioning stimulus. This produced negative values for most of the computed percentiles. // CONCLUSIONS: This study determined percentile reference values of CPM that can be used to better phenotype patients for clinical and research purposes. The negative value of percentiles suggests that a slightly negative CPM effect can be observed in pain-free volunteers. // IMPLICATIONS: Pain facilitation rather than inhibition during the conditioning stimulus occurs in some pain-free volunteers and may not necessarily represent an abnormal finding

Does Acupuncture Needling Induce Analgesic Effects Comparable to Diffuse Noxious Inhibitory Controls?

Diffuse noxious inhibitory control (DNIC) is described as one possible mechanism of acupuncture analgesia. This study investigated the analgesic effect of acupuncture without stimulation compared to nonpenetrating sham acupuncture (NPSA) and cold-pressor-induced DNIC. Forty-five subjects received each of the three interventions in a randomized order. The analgesic effect was measured using pressure algometry at the second toe before and after each of the interventions. Pressure pain detection threshold (PPDT) rose from 299 kPa (SD 112 kPa) to 364 kPa (SD 144), 353 kPa (SD 135), and 467 kPa (SD 168) after acupuncture, NPSA, and DNIC test, respectively. There was no statistically significant difference between acupuncture and NPSA at any time, but a significantly higher increase of PPDT in the DNIC test compared to acupuncture and NPSA. PPDT decreased after the DNIC test, whereas it remained stable after acupuncture and NPSA. Acupuncture needling at low pain stimulus intensity showed a small analgesic effect which did not significantly differ from placebo response and was significantly less than a DNIC-like effect of a painful noninvasive stimulus

Ultrasound anatomy of the nerves supplying the cervical zygapophyseal joints: an exploratory study

Nerve blocks and radiofrequency neurotomy of the nerves supplying the cervical zygapophyseal joints are validated tools for diagnosis and treatment of chronic neck pain, respectively. Unlike fluoroscopy, ultrasound may allow visualization of the target nerves, thereby potentially improving diagnostic accuracy and therapeutic efficacy of the procedures. The aims of this exploratory study were to determine the ultrasound visibility of the target nerves in chronic neck pain patients and to describe the variability of their course in relation to the fluoroscopically used bony landmarks

Current evidence for central analgesic effects of NSAIDs: an overview of the literature

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for a variety of painful conditions. Their peripheral anti-inflammatory effect due to inhibition of prostaglandin synthesis is well documented. In the late 1980's, animal data suggested for the first time that NSAIDs might have central effects as well. Since that time, central inflammatory and nociceptive pathways that are potential targets of NSAIDs have been extensively studied in both animal and human models. This review provides an overview of the relevant literature implicated in the central effects of NSAIDs. The role of different enzymes and mediators, as well as the central effects of NSAIDs are discussed. Literature search was performed by PubMed NCBI. A large body of evidence supports the central effects of NSAIDs in animal models of inflammatory pain conditions. Relevant mechanisms that underlie this central action involve spinal upregulation of the enzyme cyclooxygenase, increased spinal prostaglandin E2 production, modulation of inhibitory fast synaptic currents in lamina I and II of the dorsal horn, and glycine-dependent modulation of pain. Results from animal models are not yet sufficiently supported by human studies. This does not necessarily imply that the central effects of NSAIDs are irrelevant to human pain, but rather that methodological and regulatory barriers are the limiting step to translating findings from animal studies to human research protocols

Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain.

INTRODUCTION Quantitative sensory tests (QST) can be used for profiling anti-nociceptive effects of analgesics. However, anti-nociceptive effects detected by QST are not necessarily associated with analgesic effects in pain patients. As part of a large investigation on low back pain, this paper describes the immediate analgesic and anti-nociceptive effects of oxycodone in chronic low-back pain and ranks different QST according to their ability to reflect this effect. The results are expected to support the selection of QST for future studies on potential novel opioid agonists in human pain. METHODS In this randomized, placebo-controlled and double-blinded cross-over study, 50 patients with chronic low-back pain received a single oral dose of oxycodone 15mg or active placebo, and underwent multiple QST testing. The intensity of low-back pain was recorded during 2h. The areas under the ROC curves and 95% confidence intervals were determined, whereby responder status (≥30% pain reduction) was set as reference variable and changes in QST from baseline were set as classifiers. RESULTS Significant analgesic effect on low-back pain as well as anti-nociceptive effects for almost all QST parameters were observed. The QST with the highest area under the curve were heat pain detection threshold (0.65, 95%-CI 0.46 to 0.83), single-stimulus electrical pain threshold (0.64, 95%-CI 0.47 to 0.80) and pressure pain detection threshold (0.63, 95%-CI 0.48 to 0.79). CONCLUSIONS The results suggest that anti-nociceptive effects assessed by QST fairly reflect clinical efficacy of oxycodone on low-back pain. Pressure pain detection threshold, heat pain detection threshold and single-stimulus electrical pain threshold may be more suitable to sort out potential non-responders rather than identifying potential responders to opioid medication. Future pre-clinical human research may consider these results when investigating the analgesic effect of opioid agonists by means of QST