Activation of NMDA receptors in the brainstem, rostral ventromedial medulla, and nucleus reticularis gigantocellularis mediates mechanical hyperalgesia produced by repeated intramuscular injections of acidic saline in rats.
Repeated injections of acidic saline into the gastrocnemius muscle induce both muscle and cutaneous hypersensitivity. We have previously shown that microinjection of local anesthetic into either the rostral ventromedial medulla (RVM) or the nucleus reticularis gigantocellularis (NGC) reverses this muscle and cutaneous hypersensitivity. Although prior studies show that NMDA receptors in the RVM play a clear role in mediating visceral and inflammatory hypersensitivity, the role of NMDA receptors in the NGC or in noninflammatory muscle pain is unclear. Therefore, the present study evaluated involvement of the NMDA receptors in the RVM and NGC in muscle and cutaneous hypersensitivity induced by repeated intramuscular injections of acidic saline. Repeated intramuscular injections of acidic saline, 5 days apart, resulted in a bilateral decrease in the withdrawal thresholds of the paw and muscle in all groups 24 hours after the second injection. Microinjection of NMDA receptor antagonists into the RVM reversed both the muscle and cutaneous hypersensitivity. However, microinjection of NMDA receptor antagonists into the NGC only reversed cutaneous but not muscle hypersensitivity. These results suggest that NMDA receptors in the RVM mediate both muscle and cutaneous hypersensitivity, but those in the NGC mediate only cutaneous hypersensitivity after muscle insult.


CONCLUSIONS
The current study shows that NMDA receptors in supraspinal facilitatory sites maintain noninflammatory muscle pain. Clinical studies in people with chronic widespread, noninflammatory pain, similarly, show alterations in central excitability. Thus, understanding mechanisms in an animal model could lead to improved treatment for patients with chronic muscle pain.
Graduate Program in Physical Therapy and Rehabilitation Sciences, Neuroscience Graduate Program, Pain Research Program, The University of Iowa, Iowa City.
Luis F
LF
Da Silva
Josimari M
JM
Desantana
Kathleen A
KA
Sluka
D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004525:Efferent Pathways / Q000166:cytology / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007273:Injections, Intramuscular; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D008845:Microinjections; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009135:Muscular Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012154:Reticular Formation / Q000166:cytology / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D012965:Sodium Chloride / Q000009:adverse effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D012965:Sodium Chloride