Time-course of neuropathic pain in mice deficient in neuronal or inducible nitric oxide synthase

• Functional regeneration was studied in mice deficient in nNOS and iNOS.
• Mechanical pain threshold was not normalised in either strain of NOS deficient mice.
• There were no alterations in cell composition or in glutamate and μ receptor binding.
• There was a significant difference in spinal cannabinoid binding.
• NOS–cannabinoid interaction may contribute to differences in nociception.

Nitric oxide which is synthesised by nitric oxide synthase (NOS) is involved in processes related to regeneration after nerve injury and neuropathic pain. Here we investigated functional aspects of the nociceptive system. For that purpose, the chronic constriction injury (CCI) model induced by loose ligation of the sciatic nerve was employed in C57Bl/6J wild-type (WT), nNOS and iNOS knock-out (−/−) mice. Their thermal and mechanical pain thresholds were then measured over a period of six weeks. In addition, 3H-DAMGO, 3H-CP 55.940, and 3H-l-glutamate binding, and neuronal (NeuN-immunostained) and astroglial (GFAP-immunostained) cell composition were studied. There were no significant differences in cell composition between the three strains used. Significant differences between CCI and sham-operated animals were found in nNOS−/− after day 6, in WT mice after day 10, and in iNOS−/− after day 17 post surgery. The mechanical pain threshold was normalised after day 45 post surgery in WT mice only. There were no changes in DAMGO and glutamate binding. However, we found significant differences in CP 55.940 binding in the spinal cord. It was concluded that NOS–cannabinoid interaction contributes to differences in nociceptive behaviour.