Attenuation of hyperalgesia in a rat model of neuropathic pain after intrathecal pre- or post-treatment with a neurokinin-1 antagonist

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Abstract
Athecal (i.t.) injection to rats with mono-neuropathy produced by sciatic nerve constriction. Rats exhibited tactile allodynia and cold hyperalgesia over a 16-day testing period. L-732,138 (5–200 nmol) administered i.t. prior to and for 3 consecutive days post-surgery attenuated the mechanical allodynia and cold hyperalgesia on days 4 and 8 post-surgery. The effects of i.t. L-732,138 were also determined in rats with established nerve injury-induced neuropathy. The NK-1 receptor antagonist was injected for 4 consecutive days starting on day 8 post-sciatic nerve injury. Administration of L-732,138 (5–200 nmol) i.t. produced both anti-allodynic and anti-hyperalgesic effects on day 12, but the effect was not permanent, as nociceptive thresholds were similar to controls by day 16. These results demonstrate that substance P is involved both in the induction and the maintenance of neuropathic pain and provides justification for the development and administration of substance P antagonists for the management of clinical neuropathic pain....