Recurrent antinociception induced by intrathecal or peripheral oxytocin in a neuropathic pain rat model

The search for new ligands to treat neuropathic pain remains a challenge. Recently, oxytocin has emerged as an interesting molecule modulating nociception at central and peripheral levels, but no attempt has been made to evaluate the effect of recurrent oxytocin administration in neuropathic pain. Using male Wistar rats with spinal nerve ligation, we evaluated the effects of recurrent spinal (1 nmol; given by lumbar puncture) or peripheral (31 nmol; given by intraplantar injection in the ipsilateral paw to spinal nerve ligation) oxytocin administration on pain-like behavior in several nociceptive tests (tactile allodynia and thermal and mechanical hyperalgesia) on different days. Furthermore, we used an electrophysiological approach to analyze the effect of spinal 1 nmol oxytocin on the activity of spinal dorsal horn wide dynamic range cells. In neuropathic rats, spinal or peripheral oxytocin partially restored the nociceptive threshold measured with the von Frey filaments (tactile allodynia), Hargreaves (thermal hyperalgesia) and Randall-Selitto (mechanical hyperalgesia) tests for 12 days. These results agree with electrophysiological data showing that spinal oxytocin diminishes the neuronal firing of the WDR neurons evoked by peripheral stimulation. This effect was associated with a decline in the activity of primary afferent A delta- and C-fibers. The above findings show that repeated spinal or peripheral oxytocin administration attenuates the pain-like behavior in a well-established model of neuropathic pain. This study provides a basis for addressing the therapeutic relevance of oxytocin in chronic pain conditions.