A subset of μ-opioid receptor-expressing cells in the rostral ventromedial medulla contribute to thermal hyperalgesia in experimental neuropathic pain

The rostral ventromedial medulla (RVM) is a major region for the descending modulation of pain at the spinal cord level, and neurons in the RVM have been implicated in the inhibition and facilitation of spinal nociceptive transmission. Although recent studies have established that the RVM facilitation of nociceptive transmission in the spinal cord contributes to neuropathic pain, the underlying mechanisms remain largely unknown. In the present study, we investigated the effects of kainic acid (KA)-induced RVM damage on neuropathic pain behavior and the expression of molecules implicated in pain modulation. KA was injected into the RVM midline region after neuropathic pain was established by chronic constrictive injury of the left sciatic nerve. Thermal hyperalgesia, but not mechanical allodynia, was persistently suppressed in the ipsilateral paw by a single KA injection into the RVM for at least the next 7 days in a rat neuropathic pain model. KA injection alone did not affect the nocifensive responses to mechanical and thermal stimuli on the intact side. Immunohistochemical analysis revealed that KA injection into the RVM significantly reduced the number of immunoreactive neurons for μ-opioid receptors, but not tryptophan hydroxylase, in association with the analgesic effect. These results suggest that a subset of RVM neurons expressing μ-opioid receptors contribute to the maintenance of thermal hyperalgesia in neuropathic pain.

Research highlights▶ The effects of kainic acid (KA)-induced RVM damage on neuropathic pain were examined. ▶ Thermal hyperalgesia to the ipsilateral paw was suppressed by a single KA injection. ▶ Mechanical allodynia was unaffected by KA injection. ▶ The number of neurons expressing μ-opioid receptors, but not tryptophan hydroxylase, was reduced. ▶ Thermal hyperalgesia in neuropathic pain might be maintained by a RVM neuron subset.