Neuroscience 2002 Abstract
| Presentation Number: | 453.10 |
|---|---|
| Abstract Title: | suppression of inflammatory and neuropathic pain by CT-3: site of action and molecular mechanisms. |
| Authors: |
Petros, T. J.*1
; Huang, S. M.1
; Imamura, S. H.1
; Petek, K. W.1
; Bradshaw, H. B.1
; Walker, J. M.1
1Neuro/Psych, Brown University, Providence, RI |
| Primary Theme and Topics |
Sensory Systems - Pain Modulation -- Opiods, cannabinoids and other peptides and receptors |
| Secondary Theme and Topics | Sensory Systems<br />- Pain Modulation<br />-- Inflammatory pain |
| Session: |
453. Pharmacology: cannabinoids Poster |
| Presentation Time: | Tuesday, November 5, 2002 9:00 AM-10:00 AM |
| Location: | Hall A2-B3 F-41 |
| Keywords: | cannabinoid, CB1, analgesia, inflammation |
1,1-Dimethylheptyl-delta-8-THC-11-oic acid (CT-3 or ajulemic acid) is a potent analog of THC-11-oic acid (the metabolite of THC). The apparent lack of psychotropic effects of CT-3 makes it an attractive candidate for therapeutic development. Here we extended the characterization of CT-3 to models of chronic inflammatory pain and neuropathic pain in rats, and investigated the mechanisms that contribute to the unique behavioral profile of CT-3.
(1) Systemic administration of CT-3 was effective in suppressing thermal hyperalgesia in CFA-inflammed rats, and in reversing mechanical allodynia in the CCI model of neuropathic pain.
(2) Peripheral administration of CT-3 (i.pl.) and intracerebral, but not intrathecal administration were effective in suppressing CFA-induced hyperalgesia.
(3) In competition binding with [3H]SR141716A, CT-3 exhibited an approximate 4 fold higher Ki in spinal cord compared to brain membrane preparations. Likewise, in [S35]GTPgS binding assays, CT-3 behaved as a partial agonist in the brain in comparison to CP55,940, and it failed to produce G-protein stimulation in spinal cord membranes (up to 10mM).
(4) Similar amounts of CT-3 and D9-THC were found in the brain 30min following intraperitoneal (i.p.) injections, suggesting comparable accessibility of the drugs to brain receptors.
In summary: CT-3 was found to be effective in animal models of chronic inflammatory and neuropathic pain. The effects appear to be due mainly to actions of CT-3 in the brain. Its improved side-effect profile may be due to an unusual mode of action a the CB1 receptor leading to atypical effects on second messenger systems.
(1) Systemic administration of CT-3 was effective in suppressing thermal hyperalgesia in CFA-inflammed rats, and in reversing mechanical allodynia in the CCI model of neuropathic pain.
(2) Peripheral administration of CT-3 (i.pl.) and intracerebral, but not intrathecal administration were effective in suppressing CFA-induced hyperalgesia.
(3) In competition binding with [3H]SR141716A, CT-3 exhibited an approximate 4 fold higher Ki in spinal cord compared to brain membrane preparations. Likewise, in [S35]GTPgS binding assays, CT-3 behaved as a partial agonist in the brain in comparison to CP55,940, and it failed to produce G-protein stimulation in spinal cord membranes (up to 10mM).
(4) Similar amounts of CT-3 and D9-THC were found in the brain 30min following intraperitoneal (i.p.) injections, suggesting comparable accessibility of the drugs to brain receptors.
In summary: CT-3 was found to be effective in animal models of chronic inflammatory and neuropathic pain. The effects appear to be due mainly to actions of CT-3 in the brain. Its improved side-effect profile may be due to an unusual mode of action a the CB1 receptor leading to atypical effects on second messenger systems.
Supported by NIH: K02DA00375, DA13012, NS33247
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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