Abstract
Almost a half century of research has elaborated the discoveries of the central mechanisms governing the analgesic responses of opiates, including their receptors, endogenous peptides, genes and their putative spinal and supraspinal sites of action. One of the central tenets of “gate-control theories of pain” was the activation of descending supraspinal sites by opiate drugs and opioid peptides thereby controlling further noxious input. This review in the Special Issue dedicated to the research of Dr. Gavril Pasternak indicates his contributions to the understanding of supraspinal mediation of opioid analgesic action within the context of the large body of work over this period. This review will examine (a) the relevant supraspinal sites mediating opioid analgesia, (b) the opioid receptor subtypes and opioid peptides involved, (c) supraspinal site analgesic interactions and their underlying neurophysiology, (d) molecular (particularly AS) tools identifying opioid receptor actions, and (e) relevant physiological variables affecting site-specific opioid analgesia. This review will build on classic initial studies, specify the contributions that Gavril Pasternak and his colleagues did in this specific area, and follow through with studies up to the present.
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Abbreviations
- APV:
-
dl-2-Amino-5-phosphono-valerate
- AS:
-
Antisense
- BEND:
-
Beta-endorphin
- BFNA:
-
Beta-funaltrexamine
- Bupr:
-
Buprenorphine
- CCK:
-
Cholecystokinin
- DADL:
-
d-Ala2, d-Leu5-enkephalin
- DAMGO:
-
d-Ala2, MePhe4, Gly(ol)5-enkephalin
- Delt:
-
d-Ala2, Glu4 deltorphin
- DOR-1:
-
Delta opioid receptor clone
- DPDPE:
-
d-Pen2, d-Pen5-enkephalin
- DSLET:
-
d-Ser2, Leu5-enkephalin-Thr6
- EAA:
-
Excitatory amino acid
- EKC:
-
Ethylketocyclazocine
- GI:
-
Gastrointestinal
- GPCR:
-
G-protein coupled receptor
- IBNtxA:
-
39-Iodobenzoyl-6b-naltrexamide
- icv:
-
Intracerebroventricular
- it:
-
Intrathecal
- KO:
-
Knockout
- KOR-1:
-
Kappa-1 opioid receptor clone
- KOR-3:
-
Kappa-3 opioid receptor clone
- LC:
-
Locus coeruleus
- MA:
-
Mercaptoacetate
- mPFC:
-
Medial prefrontal cortex
- MOR-1:
-
Mu opioid receptor clone
- MPOA:
-
Medial preoptic hypothalamus
- M3G:
-
Morphine-3 glucuronide
- M6G:
-
Morphine-6 glucuronide
- NAC:
-
Nucleus accumbens
- NalBzoH:
-
Naloxone benzoylhydrazone
- NBNI:
-
Nor-binaltorphimine
- NE:
-
Norepinephrine
- NMDA:
-
N-methyl-d-aspartate
- NPY:
-
Neuropeptide Y
- NRGC:
-
Nucleus reticularis gigantocellularis
- NRM:
-
Nucleus raphe magnus
- NTI:
-
Naltrindole
- NTII:
-
Naltrindole isothiocyanate
- ODNs:
-
Oligodeoxynucleotides
- OFQ/N:
-
Orphanin/FQ
- PCB:
-
1-(p-Chlorobenzoyl)-piperazine-2,3-dicarboxylate
- PPENK:
-
Prepro-enkephalin
- ppOFQ/N:
-
Prepro-orphanin/FQ/nociception
- SPA:
-
Stimulation-produced analgesia
- TP:
-
Testosterone propionate
- TRH:
-
Thyrotropin-releasing hormone
- VMH:
-
Ventromedial hypothalamus
- vlPAG:
-
Ventrolateral periaqueductal gray
- VTA:
-
Ventral tegmental area
- 2DG:
-
2-Deoxy-d-glucose
- 5HT:
-
Serotonin
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Rossi, G.C., Bodnar, R.J. Interactive Mechanisms of Supraspinal Sites of Opioid Analgesic Action: A Festschrift to Dr. Gavril W. Pasternak. Cell Mol Neurobiol 41, 863–897 (2021). https://doi.org/10.1007/s10571-020-00961-9
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DOI: https://doi.org/10.1007/s10571-020-00961-9