Analgesia supraspinal

Mu Morphine-like supraspinal analgesia, respiratory and physical depression, miosis, reduced Gl motility... 

Opioid actions at a number of other supraspinal sites (thalamic levels, the amygdala and the sensory cortex) are likely to be of relevance to analgesia. 

Zhu Y, King MA, Schuller AGP, Nitsche JF, Reidl M, Elde RP, Unterwald E, Pasternak GW, Pintar JE. Retention of supraspinal delta-like analgesia and loss of morphine tolerance in opioid receptor knockout mice. Neuron 1999 24 243-252. 

Kauppila et al. 1992). The synergistic interaction between cocaine and opioid analgesia likely involves noradrenergic mechanisms, supraspinal ju and 5 receptors, and spinal ju receptors (Misra et al. 1987 Sierra et al. 1992). 

Lin Y, Morrow TJ, Kiritsy-Roy JA, Terry LC, Casey KL. (1989). Cocaine evidence for supraspinal, dopamine-mediated, non-opiate analgesia. Brain Res. 479(2) 306-12. 

Sierra V, Duttaroy A, Lutfy K, Candido J, Billings B, Zito SW, Yoburn BC. (1992). Potentiation of opioid analgesia by cocaine the role of spinal and supraspinal receptors. Life Sci. 50(8) 591-97. Smith FL, Cichewicz D, Martin ZL, Welch SP. (1998). The enhancement of morphine anti nociception in mice by delta9-tetrahydrocannabinol. Pharmacol Biochem Behav. 60(2) 559-66. 

After epidural injection, an opioid may transfer into the cerebrospinal fluid (CSF), into the blood or bind to epidural fat, the extent depending on their lipophilicity. After epidural administration, morphine passes slowly into the CSF. Sufentanil, which is highly lipid soluble, can be detected in the plasma within 2-5 minutes after epidural injection and part of the analgesic effect of the more lipid soluble opioids may be due to a supraspinal action amplifying the direct spinal action. Epidural fentanyl and sufentanil produce a more consistent and intense analgesia than morphine, with a faster onset. Flowever, the duration is short but this can be overcome by giving them by continuous epidural infusions. 

The disinhibition of PAG output neurones mediates the supraspinal analgesia of morphine and serotonin... 

The i.c.v. injection of apamin or charybdotoxin, specific blockers of the SK and BK type of Ca2+-activated K+ channels, respectively, prevented the antinociception mediated by tricyclic antidepressants and H1 histamine receptor antagonists whereas 0C2 adrenoceptor-mediated supraspinal analgesia did not depend on the activation of these K+ channels (Table 1). 

Again, as is the case for KAtp channels involved in supraspinal analgesia those participating in spinal antinociception are not tonically activated since none of the Katp channel blockers exerted any effect per se. 

In vivo studies employing tests of acute pain unequivocally showed the involvement of Katp, Kv1.1 and Ca2+-activated K+ channels in supraspinal, spinal and peripheral analgesia produced by different classes of analgesics. Furthermore, two-pore-domain and G-protein gated inward rectifier (Kir3.x) K+ channels are affected by volatile anesthetics. The latter also contribute to p- and K-opioid receptor-mediated analgesia (Ikeda et al., 2000). 

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