Harasawa I, Lai J, Porreca F, Fields HL, Meng ID (2003) Selective elimination of mu-opioid receptor expressing neurons in the rostral ventromedial medulla (RVM) does not affect periaqueductal gray (pag) stimulation-produced analgesia. Neuroscience 2003 Abstracts 177.5. Society for Neuroscience, New Orleans, LA.
Summary: PAG stimulation produces antinociception at spinal levels by modulating RVM neuronal activity. Microinjection of saporin conjugated with the mu-opioid receptor agonist dermorphin (DERM-SAP) into the RVM selectively eliminates MOR expressing neurons and diminishes neuropathic pain symptoms (Porreca et al., 2001). The aim of the present study was to determine whether MOR expressing neurons in the RVM are required for PAG stimulation produced analgesia (PAG/SPA). The minimum electrical current required to inhibit the tail flick response was compared in barbiturate-anesthetized rats given a single RVM injection of SAP or DERM-SAP 3-4 weeks prior to testing. Thresholds in SAP and DERM-SAP treated rats were not different. Furthermore, microinjection of the glutamate receptor antagonist kynurenic acid (10 mM, 800 nl) into the RVM disrupted PAG/SPA in both SAP and DERM-SAP treated rats. These results indicate that 1) mu-receptor expressing neurons in the RVM are not necessary for PAG/SPA, and 2) excitatory amino acid transmission in the RVM is critical for PAG/SPA. In additional experiments, inhibition of neurotransmitter release in the RVM by the microinjection of cobalt chloride (CoCl2, 100 mM, 800 nl), produced significant antinociception only in DERM-SAP treated rats. This finding suggests that DERM-SAP injections result in increased tonic inhibition of RVM neurons and that CoCl2 disinhibits these neurons to produce antinociception. Tonic inhibition of off-cells would account for our failure to find off-cells in DERM-SAP treated rats.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)