The neuropharmacology of centrally-acting analgesic medications in fibromyalgia.
As demonstrated above, the anatomy and neuropharmacology of the pain pathways within the CNS, even to the level of the midbrain, are extraordinarily complex. Indeed, discussions of the effects of these agents on the neuropharmacology of the thalamus, hypothalamus, and cortex were excluded from this review owing to their adding further to this complexity. Also, the dearth of data regarding FMS pain pathophysiology necessitated a relatively generic analysis of the pain pathways. As mentioned in the introduction, the current thought is that central sensitization plays an important role in FMS. However, we see in this chapter that the behavioral state of central sensitization may be a result of alterations in either the ascending systems or in one or more descending systems. Studies to assess the presence or relative importance of such changes in FMS are difficult to perform in humans, and to date there are no animal models of FMS. Accepting these limitations, it is apparent that many drugs considered to date for the treatment of FMS do target a number of appropriate sites within both the ascending and descending pain pathways. The data regarding clinical efficacy on some good candidate agents, however, is extremely preliminary. For example, it is evident from the present analysis that SNRIs, alpha 2 agonists, and NK1 antagonists may be particularly well suited to FMS, although current data supporting their use is either anecdotal or from open-label trials [114,149]. Other sites within the pain pathways have not yet been targeted. Examples of these include the use of CCKB antagonists to block on-cell activation or of nitric oxide synthetase antagonists to block the downstream mediators of NMDA activation. Efficacy of such agents may give considerable insight into the pathophysiology of FMS. Finally, as indicated previously, FMS consists of more than just chronic pain, and the question of how sleep abnormalities, depression, fatigues, and so forth tie into disordered pain processing is being researched actively. Future research focusing on how the various manifestations of FMS relate to one another undoubtedly will lead to a more rational targeting of drugs in this complex disorder.
Cypress Bioscience, 4350 Executive Drive, Suite 325, San Diego, CA 92131, USA. srao@cypressbio.com
Srinivas G
SG
Rao
D000700:Analgesics / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use*; D005356:Fibromyalgia / Q000188:drug therapy*; D006801:Humans; D009125:Muscle Relaxants, Central / Q000627:therapeutic use
D000700:Analgesics; D000927:Anticonvulsants; D000928:Antidepressive Agents; D009125:Muscle Relaxants, Central