Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury

Antagonists of glutamate receptors of the N-methyl-D-aspartate subclass (NM DAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system pl asticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in bra in and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyp eralgesia accompanying inflammation, normalized the mechanical hypersensiti vity (allodynia/hyperalgesia) produced by chemical or mechanical nerve inju ry, and reduced autotomy-like behavior and lesion size after excitotoxic sp inal cord injury. AC produced these effects in the absence of antinocicepti ve effects in acute pain tests. Endogenous AG also was detected in rodent l umbosacral spinal cord in concentrations similar to those previously detect ed in brain. The evidence suggests a unique antiplasticity and neuroprotect ive role for AG in processes underlying persistent pain and neuronal injury .