Letters to the Editor: Feedback from the Readers

Second, Dr. Clauw repeatedly points out that there is no peripheral tissue lesion in FM [admittedly, this is left a bit ambiguous by his Table 2 in Reference 1 and Figure 1 in Reference 2]. In fact, over the last 25 years, there have been numerous demonstrations of peripheral pathology involving cutaneous, muscular, and neuronal tissue in FM. Interestingly, many of these tissue findings have involved, either directly or indirectly, an aberrancy of the immune system.^6-16

Third, I and others have recently been able to show electrophysiologic and microscopic evidence of peripheral nerve injury in FM.^17-19 These changes have included evidence of a polyneuropathy involving large nerves in 47% of FM patients, and peripheral nerve demyelination, akin to that seen in chronic inflammatory demyelinating polyneuropathy (CIDP), in 33% of FM patients.¹⁷ We have also reported preliminary evidence of diminished epidermal, nerve fiber density in FM patients suggestive of a small fiber neuropathy (SFN).²⁰ These latter findings are of particular interest since SFN is known to be a painful disorder, and chronic C-fiber stimulation is thought by most, though not by all, to be a major component to the induction of CS.^21-23 SFN could thus form one source of the necessary peripheral nociceptive input required for the production of “wind up” and CS in FM. In our earliest FM series, none of these peripheral nerve changes could be explained by any other mechanism but peripheral immunologically mediated injury, and suggested to us a role for immunotherapy in selected FM patients.¹⁷ Staud et al have recently pointed out the potential importance of significant muscular injury patterns in FM and demonstrated their potential for a role in CS maintenance.⁴ In everyday rheumatologic practice (rather than during clinical research), it is also likely that other peripheral factors, including metabolic, mechanical, endocrine, and neoplastic ones, to name a few, are important in the enhanced central pain production in FM.

These considerations regarding the importance of peripheral nociceptive input in FM for the maintenance of CS are of more than academic interest. It is known, for example, that extinguishing peripheral nociceptive input effectively eliminates spinal cord “wind up” and, in the setting of dorsal horn hyperexcitability (i.e., CS), abolishes CS.^24-26 This degradation of CS may be somewhat gradual in my experience (days to weeks), presumably due to the long-term neuroplastic changes associated with CS.5,22 On the other hand, there is no experimental or practical evidence that I am aware of that shows that control of CS with “centrally acting [medicinal] agents” such as amitrptyline or pregabalin ever leads to the extinction of peripheral nociceptive input. At best, therefore, such centrally acting agents might serve as temporary or “bridge” therapy while the true nature of the peripheral, perpetuating factor(s) is uncovered and treated in FM. Borg-Stein has alluded to this strategy recently.²⁷