A nociceptive signaling role for neuromedin B.
Here we used an array-based differential screen to uncover the expression of the neuropeptide neuromedin B (NMB) in the trigeminal ganglia of mice. Double-labeling experiments reveal NMB is expressed in a subset of sensory neurons that colabel with calcitonin gene-related peptide and TRPV1 suggestive of a role for NMB in nociception. Indeed, administration of NMB antagonist greatly attenuates edema and nerve sensitization following stimulation of peripheral nerves with mustard oil, demonstrating that NMB contributes to neurogenic inflammation. Moreover, direct injection of NMB causes local swelling and nociceptive sensitization. Interestingly, we also find that the receptor for NMB is expressed in interneurons in the superficial layers of the dorsal horn. We used NMB-saporin to specifically eliminate NMBR-expressing neurons and determined they are required in responses to noxious heat, but not for reaction to mechanical and pruritic stimuli. Thus, NMB may be a neurotransmitter that is selectively involved in the perception of thermal stimuli.
Molecular Genetics Unit, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Health, National Institutes of Health, Bethesda, MD 20892, USA.
Santosh K
SK
Mishra
Sarah
S
Holzman
Mark A
MA
Hoon
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D006358:Hot Temperature; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009443:Neuritis / Q000473:pathology; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D009479:Neuropeptides / Q000096:biosynthesis; D059225:Nociception / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D020671:Posterior Horn Cells / Q000502:physiology; D018004:Receptors, Bombesin / Q000096:biosynthesis / Q000235:genetics; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology; D013373:Substance P / Q000378:metabolism
D009479:Neuropeptides; D018004:Receptors, Bombesin; D013373:Substance P; D015287:Neurokinin B; C038393:neuromedin B; D015740:Calcitonin Gene-Related Peptide