Spinal activation of the NPY Y1 receptor reduces mechanical and cold allodynia in rats with chronic constriction injury

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HIGHLIGHTSNPY and its associated receptors are implicated in pain modulation.The role of spinal Y1R activation in rats with CCI has not yet been tested.Intrathecally applied Y1R agonist reduces mechanical and cold allodynia in CCI rats.Spinal Y1R is an attractive drug target against neuropathic pain.Neuropeptide tyrosine (NPY) and its associated receptors Y1R and Y2R have been previously implicated in the spinal modulation of neuropathic pain induced by total or partial sectioning of the sciatic nerve. However, their role in chronic constrictive injuries of the sciatic nerve has not yet been described. In the present study, we analyzed the consequences of pharmacological activation of spinal Y1R, by using the specific Y1R agonist Leu31Pro34-NPY, in rats with chronic constriction injury (CCI). CCI and sham-injury rats were implanted with a permanent intrathecal catheter (at day 7 after injury), and their response to the administration of different doses (2.5, 5, 7, 10 or 20 μg) of Leu31Pro34-NPY (at a volume of 10 μl) through the implanted catheter, recorded 14 days after injury. Mechanical allodynia was tested by means of the up-and-down method, using von Frey filaments. Cold allodynia was tested by application of an acetone drop to the affected hindpaw. Intrathecal Leu31Pro34-NPY induced an increase of mechanical thresholds in rats with CCI, starting at doses of 5 μg and becoming stronger with higher doses. Intrathecal Leu31Pro34 also resulted in reductions in the frequency of withdrawal to cold stimuli, although the effect was somewhat more moderate and mostly observed for doses of 7 μg and higher. We thus show that spinal activation of the Y1R is able to reduce neuropathic pain due to a chronic constrictive injury and, together with other studies, support the use of a spinal Y1R agonist as a therapeutic agent against chronic pain induced by peripheral neuropathy.

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