Differences in peripheral endocannabinoid modulation of scratching behavior in facial vs. spinally-innervated skin

• Published in: Neuropharmacology 2012-09, Vol.63 (4), p.743-749
• Main Authors: Spradley, Jessica Marie, Davoodi, Auva, Gee, Leland Bruce, Carstens, Mirela Iodi, Carstens, E.
• Format: Article
• Language: English
• Subjects: Animals; Back; Behavior, Animal - drug effects; C-fiber; Cannabinoid receptor; Cannabinoid Receptor Agonists - therapeutic use; Cannabinoid Receptor Antagonists - adverse effects; CB1; CB2; Dermatitis, Contact - drug therapy; Dermatitis, Contact - metabolism; Dermatitis, Contact - physiopathology; Dermatitis, Contact - prevention & control; Disease Models, Animal; Endocannabinoid; Endocannabinoids - agonists; Endocannabinoids - antagonists & inhibitors; Endocannabinoids - metabolism; Face; Facial Pain - etiology; Facial Pain - prevention & control; G-protein-coupled receptor; Injections, Intradermal; Itch; Male; Molecular Targeted Therapy; Pruritus - etiology; Pruritus - prevention & control; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - metabolism; Receptor, Cannabinoid, CB2 - agonists; Receptor, Cannabinoid, CB2 - antagonists & inhibitors; Receptor, Cannabinoid, CB2 - metabolism; Scratch; Serotonin; Skin - drug effects; Skin - innervation; Skin - metabolism; Spinal Nerves - drug effects; Spinal Nerves - metabolism; Trigeminal Nerve - drug effects; Trigeminal Nerve - metabolism
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2012.05.032

Cannabinoids suppress nocifensive behaviors in rodents. We presently investigated peripheral endocannabinoid modulation of itch- and pain-related behaviors elicited from facial vs. spinally-innervated skin of rats. Intradermal (id) injection of the pruritogen serotonin (5-HT) elicited significantly more hindlimb scratch bouts, and longer cumulative time scratching, when injected in the rostral back compared to the cheek. Pretreatment of skin with inhibitors of degrading enzymes for the endocannabinoids anandamide (URB597) or 2-arachidonoylglycerol (JZL184) significantly reduced scratching elicited by 5-HT in the rostral back. These effects were prevented by co-treatment with antagonists of the CB1 (AM251) or CB2 receptor (AM630), implicating both receptor subtypes in endocannabinoid suppression of scratching in spinally-innervated skin. Conversely, pretreatment with either enzyme inhibitor, or with AM630 alone, increased the number of scratch bouts elicited by id 5-HT injection in the cheek. Moreover, pretreatment with JZL184 also significantly increased pain-related forelimb wipes directed to the cheek following id injection of the algogen, allyl isothiocyanate (AITC; mustard oil). Thus, peripheral endocannabinoids have opposite effects on itch-related scratching behaviors in trigeminally- vs. spinally-innervated skin. These results suggest that increasing peripheral endocannabinoid levels represents a promising therapeutic approach to treat itch arising from the lower body, but caution that such treatment may not relieve, and may even exacerbate, itch and pain arising from trigeminally-innervated skin of the face or scalp. ► Pruritogen-evoked scratching behavior is greater in the rostral back vs. cheek. ► Intradermal URB597 and JZL184 reduced scratching in rostral back via CB1 and CB2. ► Intradermal URB597 and JZL184 increased itch- and pain-like behaviors in the cheek. ► Endocannabinoids differentially modulate scratching dependent on skin location.