The effectiveness of spinal and systemic morphine on rat dorsal horn neuronal responses in the spinal nerve ligation model of neuropathic pain

The treatment of pain arising from nerve injury can be difficult and the op ioid sensitivity of neuropathic pain remains debatable. Clinical and animal studies report a wide range in the effectiveness of morphine, ranging from inadequate to potent analgesia. In this electrophysiological study we comp are the effectiveness of spinal versus systemic administration of morphine on the natural and electrically evoked responses of spinal neurones of rats with a selective spinal nerve (L5/6) ligation. Recordings were made 1 week and/or 2 weeks after ligation. We have also compared the effects of morphi ne, by the two routes, on normal and sham operated animals. In spinal nerve ligated rats, morphine (0.1-5 mu g) administered via the intrathecal route produced greater dose-dependent inhibitions of the neuronal responses comp ared with those produced by the systemic route (1-6 mg/kg). The dose respon se curves for intrathecal morphine on the C-fibre evoked and noxious natura l stimuli evoked neuronal responses (mechanical and thermal) of spinal nerv e ligated rats were to the left of those of sham operated and normal rats, suggesting an enhanced potency of intrathecal morphine after nerve injury. This was dearest for the lower doses of the opioid. The effects of spinal m orphine on the responses to low intensity stimuli were similar in all group s of rats. In contrast to the spinal mute, systemic morphine was less effec tive in inhibiting the evoked neuronal responses of spinal nerve ligated ra ts. This was especially clear for the C-fibre evoked and noxious natural st imuli evoked responses (mechanical and thermal) of spine nerve ligated rats . Our results suggest that the effectiveness of morphine may be partly rela ted to the timing of the treatment relative to the duration of the neuropat hy, the route of administration and also the neuropathic symptom. Spinal op ioids may be a useful approach to pain control in neuropathic pain states w here systemic routes produce inadequate analgesia, (C) 1999 International A ssociation for the Study of Pain. Published by Elsevier Science B.V.