THE ROSTROVENTROMEDIAL MEDULLA IS ENGAGED IN THE EFFECTS OF SPINAL CORD STIMULATION IN A RODENT MODEL OF NEUROPATHIC PAIN

摘要

The neurobiological mechanisms underlying the suppression of neuropathic pain by spinal cord stimulation (SCS) are still incompletely known. The present study aims at exploring whether the descending pain control system in the rostroventromedial medulla (RVM) exerts a role in the attenuation of neuropathic pain by SCS. Experiments were performed in the rat spared nerve injury (SNI) pain model. The effects of SCS on neuronal activity of pronoci-ceptive ON-like, antinociceptive OFF-like, and neutral cells, including 5-HT-like cells, in the RVM were analyzed in SCS responding and SCS non-responding SNI animals as well as in naive controls. Decreased spontaneous activities in OFF-like cells and increased spontaneous activities in ON-like cells were observed in SNI animals, whereas the spontaneous activities of 5-HT-like and neutral cells were unchanged. SCS produced a prominent increase in the discharge of OFF- and 5-HT-like cells in SCS responding, but not in non-responding SNI animals or controls. Discharge rates of ON-like and neutral cell were not affected by SCS. In awake SNI animals, microinjection of a GABA_A receptor agonist, muscimol, into the RVM significantly attenuated the antihypersensitivity effect induced by SCS while a non-selective opioid receptor antagonist, naltrexone, was ineffective. It is concluded that SCS may shift the reciprocal inhibitory and facilitatory pain modulation balance controlled by the RVM in favor of inhibition. This increase in the descending antinociceptive effect operates in concert with segmental spinal mechanisms in producing pain relief.