Opioid Modulation of Facial Itch- and Pain-related Responses and Grooming Behavior in Rats

Abstract

Intradermal facial injections of pruritogens or algogens elicit distinct behavioral hindlimb scratch or forelimb wiping responses in rodents. We systematically investigated the parameters and opioid modulation of these evoked behaviors and spontaneous facial grooming in rats. Serotonin (5-HT) elicited hindlimb scratch bouts with few wipes. Scratching was attenuated by the µ-opiate antagonist naltrexone but not morphine. In contrast, cheek injection of mustard oil (allyl-isothiocyanate (AITC)) elicited ipsilateral forelimb wipes but little hindlimb scratching. AITC-evoked wiping was significantly attenuated by morphine but not naltrexone. Spontaneous facial grooming by the forepaws was attenuated by naltrexone, whereas morphine did not affect grooming behavior before or after cheek injections of 5-HT or AITC. These data validate that the rodent "cheek" model discriminates between itch- and pain-related behaviors. Naltrexone sensitivity of facial grooming and 5-HT-evoked scratch-ing suggests a common functionality. Forelimb wipes may represent a nocifensive response akin to rubbing an injury to relieve pain.

Itch elicited by intradermal injection of serotonin, intracisternal injection of morphine, and their synergistic interactions in rats

“…We show that naloxone reduces the number of scratch bouts elicited by serotonin, a finding which has been previously shown for opioid receptor antagonists naloxone (Hachisuka et al, 2010) and naltrexone (Spradley et al, 2012). μ-Opioid receptor antagonists have been used to reduce itch produced by several pruritogens in a variety of human conditions (Phan et al, 2010).…”

“…Both behaviors were directed to the site of injection. This distinction between itch-evoked scratching and pain-evoked wiping has been replicated using an array of other pruritogens and algogens in mice (Akiyama et al, 2010; Wilson et al, 2011) and rats (Klein et al, 2011; Spradley et al, 2012). …”

“…Spradley et al (2012) showed that the μ-opioid receptor antagonist naltrexone reduced scratching caused by facial application of pruritogens, whereas morphine reduced wiping caused by algogens in rats. This finding suggests that μ-opioid receptor activation has opposite effects on processing of itchy versus painful stimuli applied to the cheek.…”

Behavioral model of itch, alloknesis, pain and allodynia in the lower hindlimb and correlative responses of lumbar dorsal horn neurons in the mouse

“…Intraplantar injection of capsaicin elicited licking behavior in rats (Klein et al, 2011a), and hindpaw injection of formalin elicited licking in mice (Hagiwara et al, 1999). We previously reported that systemic administration of morphine suppressed forelimb wiping, but not hindlimb scratching, elicited by id cheek injections of capsaicin or mustard oil in mice and rats, consistent with the notion that forelimb wiping reflects pain (Akiyama et al, 2010c; Spradley et al, 2012a). Presumably, licking of the hindpaw or forelimb wiping directed to the cheek represent the biomechanically available nocifensive responses to ameliorate chemogenic pain in these two different body areas.…”

Itch Mechanisms and Circuits

“…Recently, LaMotte’s group (119) modified the traditional model to establish the “cheek injection model.” They reported that mice exhibit distinct behaviors in response to cheek injection of pruritogens versus algogens: Pruritogens elicit scratching with the hind paw, whereas algogens evoke facial wiping with the forelimb. This model was amended in rats by Carstens’ group (127) and provides a reliable means of distinguishing itch and pain behaviors.…”