Pentoxifylline, a non-specific
cytokine inhibitor, has shown to be beneficial in inflammatory
pain in both experimental and clinical studies. The present study demonstrates for the first time, to our knowledge, the antihyperalgesic effect of
pentoxifylline in the
neuropathic pain using L5 spinal nerve transection rat model. In a preventive paradigm,
pentoxifylline (12.5, 25, 50, or 100mg/kg intraperitoneally) was administered systemically daily, beginning 1h prior to nerve transection.
Pentoxifylline (50, or 100mg/kgi.p.) produced significant decrease in the mechanical and
thermal hyperalgesia. However,
pentoxifylline (100mg/kgi.p.) did not influence the paw pressure thresholds and paw withdrawal latency in
sham-operated rats. In order to understand the possible antinocicieptive effect of
pentoxifylline in
neuropathic pain, we examined the level of
TNFalpha, IL-1beta,
IL-6 and
IL-10 protein in the contralateral brain on day 7 post-transection.
Pentoxifylline administration resulted in a dose-dependent reduction of the production of proinflammatory
cytokines like
TNFalpha, IL-1beta and
IL-6, and enhancement of
IL-10. Furthermore, we investigated the activity of
nuclear factor kappa B (
NF-kappaB) in the contralateral brain on days 7 after surgery. In accordance with the change of proinflammatory
cytokines,
Pentoxifylline (50 or 100mg/kg) significantly inhibited the activation of
NF-kappaB in the brain. This research supports a growing body of literature emphasizing the importance of
neuroinflammation and neuroimmune activation in the development of
neuropathic pain states, and the potential preventive value of
pentoxifylline in the treatment of
neuropathic pain.