Special Communications: Letter to the Editor
I read with great interest the recent article by Rand about complex regional pain syndrome (CRPS) in a recent issue of Current Sports Medicine Reports (6). Recent studies into the etiology and evolution of CRPS have reported a number of interesting results. One such aspect has been the evolving role of chemical mediators such as cytokines in the evolution and progression of CRPS.
For instance, recent studies suggest that a number of chemical modulators such as IL-1β and the calcitonin gene-related peptide (CGRP) play a major role in the progression of CRPS (1,2). Similarly, Sabsovich et al., in a recent study involving tibia fracture models, have shown that TNF-α is another significant mediator of CRPS (7). TNF-α performs this role in part by upregulating the cellular expression of the transient potential receptor vanilloid type 1 (TRPV1) (5). The quantitative number of TNF-α positive mast cells in neural tissue is attenuated significantly following systemic administration of steroids such as triamcinolone (4). Similarly, the past year has seen a rapid increase in the clinical application of the TNF inhibitors such as etanercept for the successful treatment of CRPS (3). Pentoxifylline is another agent that recently has been shown to decrease the production of local nociceptive cytokines in patients with CRPS (9).
Another recent discovery has been the role of nerve growth factor in the modulation of nociceptive stimuli in CRPS (2). In fact, it is not surprising that a marked decline in CGRP as well as nociceptive stimulation is noted after administration of anti nerve growth factor antibodies (8).
These examples clearly illustrate the important role that TNF-α and nerve growth factor play in accentuation of nociception in CRPS. There is a clear need for further studies to find new agents to modulate the effects of these agents so that patients with CRPS can have a bright and pain-free existence.
Shailendra Kapoor, M.D.
11416 Gregsby Chapel Rd., Ste. 105,
Knoxville, TN 37923
1. Angst MS, Clark JD, Carvalho B, et al. Cytokine profile in human skin in response to experimental inflammation, noxious stimulation, and administration of a COX-inhibitor: a microdialysis study. Pain
. 2008; 139:15-27.
2. Birklein F, Schmelz M. Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS). Neurosci. Lett
. 2008; 437:199-202.
3. Dahl E, Cohen SP. Perineural injection of etanercept as a treatment for postamputation pain. Clin. J. Pain
. 2008; 24:172-5.
4. Hayashi R, Xiao W, Kawamoto M, Yuge O, Bennett GJ. Systemic glucocorticoid therapy reduces pain and the number of endoneurial tumor necrosis factor-alpha (TNFalpha)-positive mast cells in rats with a painful peripheral neuropathy. J. Pharmacol. Sci
. 2008; 106:559-65.
5. Khan AA, Diogenes A, Jeske NA, et al. Tumor necrosis factor alpha enhances the sensitivity of rat trigeminal neurons to capsaicin. Neuroscience
. 2008; 155:503-9.
6. Rand SE. Complex regional pain syndrome in the adolescent athlete. Curr. Sports Med. Rep
. 2009; 8:285-7.
7. Sabsovich I, Guo TZ, Wei T, et al. TNF signaling contributes to the development of nociceptive sensitization in a tibia fracture model of complex regional pain syndrome type I. Pain
. 2008; 137:507-19.
8. Sabsovich I, Wei T, Guo TZ, et al. Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional pain syndrome type I. Pain
. 2008; 138:47-60.
9. Wei T, Sabsovich I, Guo TZ, et al. Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome. Eur J. Pain
. 2009; 13:253-62.