Aim of the study: The current study was aimed to investigate the
neuropathic pain attenuating mechanism of
pregabalin using chronic constriction injury (CCI) model in rats. Material and Methods: The sciatic nerve was ligated by placing four loose
ligatures around it to induce
neuropathic pain. The
pain development in terms of cold
allodynia, mechanical hyperalgesia, and heat
hyperalgesia was assessed on the 7th and 14th day after surgery, using
acetone drop, pinprick, and hot plate tests. On the 14th day after the injury,
pain parameters were assessed 30 minutes after administration of
pregabalin (30 mg/kg) and
sodium nitroprusside (5 mg/kg) in CCI-subjected rats. Results: CCI led to induction of
neuropathic pain, which was more prominent on 14th day in comparison to 7th day. A single administration of
pregabalin and
sodium nitroprusside on 14th day, markedly reduced
pain parameters and increased serum
nitrite levels. Pretreatment with
L-NAME abolished
neuropathic pain attenuating effects of
pregabalin suggesting that
pregabalin may increase the levels of
nitric oxide to mitigate
neuropathic pain. Pretreatment with
naloxone significantly abrogated
pain attenuating effects of
pregabalin and
sodium nitroprusside in CCI-subjected rats suggesting that
pregabalin and
nitric oxide-mediated
analgesic action are mediated through release of endogenous
opioids. Moreover,
naloxone failed to modulate
pregabalin-induced increase in
nitric oxide levels suggesting that the
opioid system does not control the
nitric oxide levels, and
opioids may be downstream modulators of
nitric oxide. Conclusion:
Pregabalin may increase the release of
nitric oxide, which may increase the release of endogenous
opioids to attenuate
neuropathic pain in CCI subjected rats.