Presynaptic localization of the carboxy-terminus epitopes of the μ opioid receptor splice variants MOR-1C and MOR-1D in the superficial laminae of the rat spinal cord
Section snippets
Perfusion and tissue processing
The procedures used in these studies were approved by the Institutional Animal Care and Use Committee of Cornell University Medical College and of the Memorial Sloan Kettering Cancer Center. All efforts were made to prevent animal suffering and to use the minimum number of animals needed to make sound scientific conclusions. For electron microscopy studies, male Sprague–Dawley rats (300–400 g; n=3; Charles River Laboratories, Wilmington, MA, USA) were deeply anesthetized with sodium
MOR-1C and MOR-1D distributions in the superficial dorsal horn
The light microscopic distribution of MOR-1C-LI and MOR-1D-LI examined in this study is illustrated in Fig. 1. In the spinal cord (Fig. 1A), MOR-1C was mainly found in the superficial laminae where it was located primarily in punctate profiles (Fig. 1B) that we show correspond to axon terminals at the ultrastructural level. We also observed MOR-1C-LI thin beaded processes in laminae V–VI and in lamina X (Abbadie et al., 2000c).
The superficial laminae of the spinal cord contained the highest
Discussion
In the superficial laminae of the dorsal horn, the majority of MOR-1C and MOR-1D-LI profiles were myelinated axons, unmyelinated axons or axon terminals. This distribution contrasts with that of MOR-1-LI which is frequently found in dendrites and soma, as well as in axons, in the same region. We also found that one third of MOR-1C-LI terminals contain dense core vesicles, indicating that this splice variant might play a role in presynaptic inhibition of neurotransmitter release from
Conclusion
We showed that two distinct splice variants of MOR-1, MOR-1C and MOR-1D, were localized in myelinated axons, unmyelinated axons or axon terminals in the superficial laminae of the dorsal horn. This distribution contrasts with that of MOR-1-LI which in the same region is frequently found in dendrites and soma as well as in axons. We also found that one third of MOR-1C-LI terminals contain dense core vesicles, indicating that this splice variant might play a role in presynaptic inhibition of
Acknowledgements
We thank Theresa Zhou, Sarita Sharma and Alla Goldberg for technical assistance. This work was supported, in part, by grants (DA02615 and DA7242) and a Senior Scientist Award to G.W.P. (DA00220) from the National Institute on Drug Abuse, a core grant from the National Cancer Institute to MSKCC (CA08748) and a grant from the National Institute of Dental and Craniofacial Research (DE 12640) to S.A.A.
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2019, NeuropharmacologyCitation Excerpt :Although the precise mechanisms by which MMG22 reduces hyperalgesia is not clear, recent studies (Akgün et al., 2019) suggest that spinal astrocytes are one of the likely targets of i.t. MMG22, given that the specific astrocyte toxin, L-α aminoadipipic acid (LAA), selectively reduced antinociception of MMG22 in inflamed mice. Both MOR and mGluR5 are found on the peripheral and central terminals of primary afferent nociceptors (Abbadie et al., 2001; Bhave et al., 2001; Jia et al., 1999; Pitcher et al., 2007), post-synaptically on neurons in the superficial dorsal horn, and on astrocytes (Abbadie et al., 2001; Coggeshall and Carlton, 1997; Huang et al., 2005; Jia et al., 1999; Pitcher et al., 2007; Valerio et al., 1997; Vidnyánszky et al., 1994). It has been reported that antagonism of cancer-mediated pain associated with upregulated mGluR5 is decreased by the administration of a selective mGluR5 antagonist (Ren et al., 2012).
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Present address: Neurological Sciences Institute, Oregon Health Sciences University, 1120 North West 20th Avenue, Portland, OR 97209, USA.