Differences in peripheral endocannabinoid modulation of scratching behavior in facial vs. spinally-innervated skin.
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.
Department of Neurobiology, Physiology & Behavior, University of California, One Shields Avenue, Davis, CA 95616-8519, USA.
Jessica Marie
JM
Spradley
Auva
A
Davoodi
Leland Bruce
LB
Gee
Mirela Iodi
MI
Carstens
E
E
Carstens
D000818:Animals; D001415:Back; D001522:Behavior, Animal / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use; D063387:Cannabinoid Receptor Antagonists / Q000009:adverse effects; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005145:Face; D005157:Facial Pain / Q000209:etiology / Q000517:prevention & control; D007271:Injections, Intradermal; D008297:Male; D058990:Molecular Targeted Therapy; D011537:Pruritus / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D013127:Spinal Nerves / Q000187:drug effects / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000187:drug effects / Q000378:metabolism*
D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; C543264:Cnr1 protein, rat; C469526:Cnr2 protein, rat; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2