Functional roles of neuromedin B and gastrin‐releasing peptide in regulating itch and pain in the spinal cord of primates

Abstract

Neuromedin B (NMB) has been demonstrated to elicit itch and pain in rodents. However, the functional role of NMB and its cognate receptor (NMBR) in regulating itch and pain in the primate spinal cord is unknown. The aim of this study was to determine the functional profile of spinal NMB and compare its behavioral effects with those elicited by spinal gastrin‐releasing peptide (GRP) in rhesus monkeys (Macaca mulatta). Following intrathecal administration, GRP (3–10 nmol) dose‐dependently elicited robust scratching responses. In contrast, intrathecal NMB (30–200 nmol) only elicited mild scratching responses. Intrathecal GRP‐ and NMB‐elicited scratching activities were attenuated by a GRP receptor (GRPR) antagonist (RC‐3095) and a NMBR antagonist (PD168368), respectively. Unlike intrathecal substance P (100 nmol) producing thermal allodynia manifested as a reduced tail‐withdrawal latency in 46C water, intrathecal administration of GRP or NMB (1–100 nmol) did not change the thermal nociceptive threshold of primates. In addition, intrathecal administration of a mu opioid receptor agonist, DAMGO (3 nmol), inhibited capsaicin‐induced thermal allodynia. Unlike DAMGO, both RC‐3095 and PD16838 (100–300 nmol) intrathecally did not produce antiallodynic effects. Taken together, these pharmacological findings indicate that spinal NMB‐NMBR and GRP‐GRPR systems have a minimum role in the neurotransmission of pain and both spinal GRPR and NMBR function independently to elicit itch/scratching responses in primates.Support or Funding InformationThe US‐PHS grants AR064456 and AR069861