Browsing by Subject "Cannabinoids"

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    Cannabinoid modulation of nociception and nociceptor activity during inflammation.
    (2009-06) Potenzieri, Carl Robert
    Previous studies have demonstrated that peripherally-administered cannabinoids at the site of injury produce antinociception in animal models of acute and persistent pain. Peripheral cannabinoid one (CB1) receptor-mediated antinociception has been attributed to CB1 receptors located on nociceptive DRG neurons and their peripheral nerve terminals. Although these studies suggest that activation of peripheral CB1 receptors located on nociceptive nerve terminals produces antinociception, how cannabinoids modulate nociceptor activity is not known. The overall aim of this thesis was to relate the behavioral antinociceptive effects of locally-administered cannabinoids with changes in the response properties of nociceptors during non-inflamed and inflamed conditions. It was hypothesized that activation of peripheral CB1 receptors attenuated nociception and nociceptor activity only during inflammation. In behavioral studies, intraplantar administration of complete Freund's adjuvant (CFA), but not saline, produced mechanical allodynia, mechanical hyperalgesia, and heat hyperalgesia. Activation of peripheral CB1 receptors produced antiallodynia and antihyperalgesia following inflammation, but did not alter nociception during non-inflamed conditions. In electrophysiological studies, only cutaneous nociceptors (Adelta and C) from inflamed skin were sensitized, and not Abeta mechanoreceptors. Local administration of CB1 receptor agonists attenuated mechanically-evoked responses of Adelta nociceptors from inflamed skin, but did not alter the evoked responses of Adelta nociceptors from non-inflamed skin. The responses of C nociceptors and Abeta mechanoreceptors from either non-inflamed or inflamed skin were not altered following local administration of cannabinoids. Our results demonstrated that peripherally-mediated cannabinoid antinociception through CB1 receptors is mediated, at least in part, by attenuation of Adelta nociceptor activity. The results from the present studies suggest that peripherally-acting CB1 receptor agonists could be administered alone or co-administered with other analgesic drugs to treat acute and persistent pain in humans and animals.
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    Pain relief of cannabinoids in the KATP pathway and its connections to the opioid pathway in mice
    (2019) Messerschmidt, Lauren; Klein, Amanda
    Opioids are known to be addictive drugs, and long term use may lead to overdose or death. To combat the opioid epidemic, different therapies should be developed and used for pain management. One potential alternative to prescription opioids is cannabis. The science of cannabinoids, the chemical compounds in cannabis, is relatively new research. There are two primary cannabinoid receptors: CB1 and CB2, both being G protein coupled receptors (Pertwee, 2006). The receptors are especially sensitive to THC and cannabidiol, both components in cannabis, which are thought to aid in pain relief. The hypothesized pathway begins with a cannabinoid binding to its receptor, which inhibits adenylyl cyclase. Adenylyl cyclase is responsible for producing cyclic adenylyl phosphate (cAMP) from ATP. Inhibiting adenylyl cyclase decreases the concentration of cAMP, resulting in the opening of ATP sensitive potassium channel opening (K ATP channels, Pertwee, 2006). This aligns with an accepted pathway for opioid signal transduction (Figure 2), and it is possible cannabinoids and opioids affect the same downstream potassium channels. In this research, experimentation of mice was used to observe the potassium channel connections between the opioid and cannabinoid pathways. This was the starting point in finding a potentially safer therapy than opioids but with similar pain relief efficacy.