Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons.
The rostral ventromedial medulla (RVM) exerts both inhibitory and excitatory controls over nociceptive neurons in the spinal cord and medullary dorsal horn. Selective ablation of mu-opioid receptor (MOR)-expressing neurons in the RVM using saporin conjugated to the MOR agonist dermorphin-saporin (derm-sap) attenuates stress and injury-induced behavioral hypersensitivity, yet the effect of RVM derm-sap on the functional integrity of the descending inhibitory system and the properties of RVM neurons remain unknown. Three classes of RVM neurons (on-cells, off-cells, and neutral cells) have been described with distinct responses to noxious stimuli and MOR agonists. Using single unit recording in lightly anesthetized rats, RVM neurons were characterized after microinjections of derm-sap or saporin. Derm-sap treatment resulted in a reduction in on-cells and off-cells when compared to saporin controls (P < 0.05). The number of neutral cells remained unchanged. After derm-sap treatment, RVM microinjections of the glutamate receptor agonist homocysteic acid increased tail-flick latencies, whereas the MOR agonist DAMGO had no effect. Furthermore, electrical stimulation of the periaqueductal gray produced analgesia in both derm-sap and saporin controls with similar thresholds. Microinjection of kynurenic acid, a glutamate receptor antagonist, into the RVM disrupted periaqueductal gray stimulation-produced analgesia in both saporin-treated and derm-sap-treated rats. These results indicate that MOR-expressing neurons in the RVM are not required for analgesia produced by either direct or indirect activation of neurons in the RVM.
Department of Neurology, University of California, San Francisco, CA, USA RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Saitama, Japan Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan Department of Pharmacology, College of Medicine, University of Arizona, Health Sciences Center, Tucson, AZ, USA Department of Biomedical Sciences, College of Osteopathic Medicine, and the Center for Excellence in the Neurosciences, University of New England, Biddeford, ME, USA.
Ichiro
I
Harasawa
Joshua P
JP
Johansen
Howard L
HL
Fields
Frank
F
Porreca
Ian D
ID
Meng
D000698:Analgesia / Q000379:methods*; D000818:Animals; D004558:Electric Stimulation; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012503:Saponins / Q000008:administration & dosage
D017450:Receptors, Opioid, mu; D012503:Saponins