Sensitization Mechanisms for Maintaining Persistent Pain Conditions

How does peripheral impulse input interact with central sensitization mechanisms to induce and maintain persistent pain conditions, including complex regional pain syndrome, irritable bowel, and fibromyalgia syndromes? Donald Price, PhD, professor in the Division of Neuroscience, Oral and Maxillofacial Surgery, University of Florida, explored this question in his plenary lecture, “Maintenance of Central Sensitization by Tonic Peripheral Impulse Input: A Common Mechanism of Complex Regional, Irritable Bowel, and Fibromyalgia Syndromes,” delivered Friday, May 7, at the American Pain Society 29th Annual Scientific Meeting.

Price spent the first half of the session discussing study results showing that IBS patients who were subjected to thermal pain stimulation demonstrated viscerosomatic convergence and facilitation, reported much higher levels of somatic pain compared to normal controls, experienced ongoing spontaneous pain not accompanied by signs of physical trauma, and exhibited enhanced afferent processing in brain levels of response to thermal stimulation of the feet.

The second half of the session focused on fibromyalgia, which Price defined as “a condition of widespread musculoskeletal pain, characterized by lowered pain thresholds in at least 11 of 18 standard tender points and by ongoing pain in upper/lower and bilateral areas of the body.”

Price discussed results from a study that showed that patients with FM exhibit enhanced “wind up” in comparison to age/sex matched normal controls, which Price said “is one indication of central sensitization in FM patients.” Yet, when FM patients and normal control groups were equated for wind up by adjusting the stimulus temperatures in the study, the FM patients had “much stronger and longer lasting ‘after sensations,’” which Price said was a further indication of central sensitization.

Study results from Staud et al. showing that rest consistently reduced and exercise consistently enhanced ongoing FM pain, provide “indirect evidence for peripheral impulse input in FM.” In another study, local anesthesia applied to one muscle tender point “reduced distal heat hyperalgesia in patients with fibromyalgia.” In the study, heat stimuli was applied to the central forearm before or after patients got placebo saline or lidocaine; the injections were administered so slowly that patients couldn’t detect which drug they had received. The lidocaine injections produced elevation in normal mechanical pain threshold.

Study participants received thermal temperature stimulation to the forearm to “evoke a pain rating of 4,” The investigators reported that “significantly lower temperatures were needed to evoke a response in FM patients, reflecting secondary hyperalgesia.” Local lidocaine -- but not placebo -- reduced secondary hyperalgesia in FM patients but produced no effect in normal controls.

Price summarized these findings by noting that tonic peripheral impulse input induces and maintains central sensitization in at least some forms of chronic regional pain syndrome, IBS, and fibromyalgia. Study results showing secondary heat hyperalgesia in IBS and FM reflect “central sensitization that is dynamically maintained by peripheral input.” Local anesthesia of one tissue source — “somatic foci in CRPS, rectum in IBS, and trapezius muscle in FM” -- can “reduce or abolish secondary hyperalgesia (or allodynia) at distant sites.” These effects are “neither the result of placebo nor systemic absorption of lidocaine."

Finally, Price stated that “Therapies directed toward these pain conditions should consider the critical roles of peripheral impulse input, central sensitization, and the powerful influence of psychological modulation (eg, placebo and nocebo factors)."