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Emerging Concepts in the Neurobiology of Pain: Evidence of Abnormal Sensory Processing in Fibromyalgia ', Mayo Clin Proc 1999; 74: 385-398 by Robert M

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Emerging Concepts in the Neurobiology of Pain: Evidence of Abnormal Sensory Processing in Fibromyalgia ', Mayo Clin Proc 1999; 74: 385-398 by Robert M Electrodiagnosis & Rehabilitation Associates– Experience and Expertise brings Excellence 2 Review of a Review Article: 'Emerging Concepts in the Neurobiology of Pain: Evidence of Abnormal Sensory Processing in Fibromyalgia ', Mayo Clin Proc 1999; 74: 385-398 by Robert M. Bennett, M. D.; reviewed by Edgar S. Steinitz, M. D. In chronic pain, the correlation between tissue pathology and the severity of pain is poor or absent. There is now solid understanding of the scientific basis for chronic pain states sustained by changes in the central nervous system (CNS), and particularly within the dorsal horn of the spinal cord where augmented and dysfunctional sensory processing occurs from sensitized neurons and primed neural networks. The concept of 'nonnocioceptive pain' (NNP), pain absent tissue damage, has now been refined at a physiologic, structural and molecular level. Dramatic structural and neurochemical changes occur even in the absence of tissue damage, a process known as 'neuroplasticty'. Fibromyalgia (FM) is an excellent model to better understand diffuse chronic pain states. To comprehend chronic pain, one must integrate both the sensory and affective-evaluative/psychological elements of the pain experience. Focusing exclusively on either alone is equally misguided. SENSORY COMPONENT OF CHRONIC PAIN Pain is the perceptual result of impulses that originate from peripheral nocioceptors which ascends into the brainstem and cerebral cortex eventuating in a pain experience, with then reflexive behavior aimed at eliminating it. Distinct differences have been found in pain threshold using a spring-loaded dolorimeter (a quantitative pressure measuring device) over tender points between FM and control subjects (80 units vs. 160 units; p = 0.002), best explained by changes in central processing especially at the spinal level. Repetitious stimulation of peripheral nerves results in a progressive increase of electrical responses recorded in second order dorsal horn neurons, termed ‘wind-up’, and a key mechanism sustaining chronic pain. The biochemical processes are dependent on activation of N-Methyl-D-Aspartate (NMDA) receptors (figure 1). There probably is also a defect in the descending spinal inhibitory antinociceptive pathways originating in the brainstem. The ‘down-regulating’ neurotransmitters involve g-aminobutric acid and met-enkephalin. Inhibition of this modulatory system may activate silent intraspinal synapses resulting in pain amplification and expansion of receptive fields. Down-regulation of pain threshold by transcutaneous electrical nerve stimulation (TENS) is well known, but while tonic stimulation normally increases pain threshold, not in FM, supporting a defect of inhibitory control. 'NNP' involves disproportionate ‘up-regulation’ and augmented sensory processing: Pain elicited by stimulation of nonnocioceptors not usually painful Central sensitization induced by past or ongoing nociception Alteration of second order dorsal column wide dynamic neurons (WDN) which magnify sensory input as pain Expansion and exaggeration of receptive fields far beyond the original distribution of nociception Activity from golgi tendon organs and muscle spindles activates pain related central neurons once sensitized Activation of NMDA receptors has a permissive effect on substance P release which readily diffuses in the dorsal horn sensitizing other cells at a distance explaining boundary expansion NMDA receptor activation results in dramatic structural changes in the dendrites having substance P receptor sites. There is a three- old increase in spinal fluid levels of substance P in FM compared with controls Animal models implicate substance P causing excessive pain reaction to noxious stimulation supporting central sensitization in the pathogenesis of FM Sensory input from muscle spindles and golgi tendon organs is a much more potent effector of sensitization, as opposed to skin, and provides incite into the prominence of muscle pain in FM It is known that motor vehicle accidents associated with whiplash injury results in a 22% prevalence of FM, vs. only 1% after accidents resulting in leg fractures Figure 1. Repetitive stimulation of unmyelinated nociceptors results in a progressive increase in discharge from second order neurons in the spinal cord. The response is not linear but cumulative. Treating with an NMDA receptor antagonist abolishes 'wind-up'. RELEVANCE OF NNP When after extensive investigations there is no organic lesion, do not miscategorize the problem as "nonorganic", a term equated with a psychogenic/somatization disorder, or malingering, but rather as 'NNP'. Furthermore, those unaware, may order expensive or risky tests, or wrongly treat as if it were nociceptive with surgery. The author believes that a medical condition should not be classified as a psychiatric disorder. MANAGEMENT LESSONS FROM THE NEUROBIOLOGY OF CHRONIC PAIN Untreated chronic pain has devastating consequences and is sustained by central sensitization. Opioids are highly effective for most chronic pain states, and those who condemn its use in severe FM, is due to ignorance. Although physical dependence is an inevitable consequence to continued use, addiction is rare, which should not be confused with "pseudo-addiction", a behavior generated attempting to obtain appropriate pain relief in the face of under treatment. Complex cases should be managed in a multidisciplinary pain clinic setting. 'PNT'/PERCUTANEOUS NEUROMODULATION THERAPY ‘PNT’ is believed to interrupt development of , or infer with, the self-sustaining mechanisms of ‘NNP’. Since our involvement as a clinical research site for ‘PNT’, sponsored by Vertis NS, the unit has now gained full FDA approval in the management of chronic lower back pain. We are proud to be the first practice in the Northwest incorporating 'PNT' therapy into our treatment of select patients ! We are delighted to announce the joining of our newest Associate, Chan S. Hwang, M. D. .
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