Facial injections of pruritogens or algogens elicit distinct behavior responses in rats and excite overlapping populations of primary sensory and trigeminal subnucleus caudalis neurons

Abstract

Klein A, Carstens MI, Carstens E. Facial injections of pruritogens or algogens elicit distinct behavior responses in rats and excite overlapping populations of primary sensory and trigeminal subnucleus caudalis neurons. J Neurophysiol 106: 1078 -1088. First published June 8, 2011 doi:10.1152/jn.00302.2011In the present study, we investigated whether intradermal cheek injection of pruritogens or algogens differentially elicits hindlimb scratches or forelimb wipes in Sprague-Dawley rats, as recently reported in mice. We also investigated responses of primary sensory trigeminal ganglion (TG) and dorsal root ganglion (DRG) cells, as well as second-order neurons in trigeminal subnucleus caudalis (Vc), to pruritic and algesic stimuli. 5-HT was the most effective chemical to elicit dose-dependent bouts of hindlimb scratches directed to the cheek, with significantly less forelimb wiping, consistent with itch. Chloroquine also elicited significant scratching but not wiping. Allyl isothiocyanate (AITC; mustard oil) elicited dose-dependent wiping with no significant scratching. Capsaicin elicited equivalent numbers of scratch bouts and wipes, suggesting a mixed itch and pain sensation. By calcium imaging, ϳ6% of cultured TG and DRG cells responded to 5-HT. The majority of 5-HT-sensitive cells also responded to chloroquine, AITC, and/or capsaicin, and one-third responded to histamine. Using a chemical search strategy, we identified single units in Vc that responded to intradermal cheek injection of 5-HT. Most were wide dynamic range (WDR) or nociceptive specific (NS), and a few were mechanically insensitive. The large majority additionally responded to AITC and/or capsaicin and thus were not pruritogen selective. These results suggest that primary and second-order neurons responsive to pruritogens and algogens may utilize a population coding mechanism to distinguish between itch and pain, sensations that are behaviorally manifested by distinct hindlimb scratching and forelimb wiping responses.

Effects of scratching and other counterstimuli on responses of trigeminothalamic tract neurons to itch-inducing stimuli in rats

“…As a result, in the present studies, 5-HT (10 l, 47 mM; Sigma) was the first pruritogen intradermally injected. Injections of this dose of 5-HT produce robust scratching and little wiping in awake rats (Klein et al 2011;Moser and Giesler 2014a). Criteria for a response to injection of a pruritogen included 1) firing rates following injection of a pruritogen Ն150% of those seen during the 1 min preceding the injections, 2) firing rates following injection of a pruritogen Ն150% of those induced by injection of vehicle, and 3) firing rate increases endured for at least 1 min.…”

“…The termination of a pruriceptive response was defined as the time at which firing returned to the mean baseline firing level. In one case, 5-HT failed to induce a response; for this neuron, the partial pruritogen histamine (10 l, 900 mM; Sigma) was intradermally injected (Klein et al 2011). All injections were separated by Ն5 mm within the receptive field.…”

“…Sensory processing related to the cheek of rodents is of particular interest because, unlike much of the rest of the body of rodents, injections of algogens and pruritogens into the cheek produce easily distinguished behavioral responses (Klein et al 2011;Moser and Giesler 2014a;Shimada and LaMotte 2008). In rats, a large percentage of VcTT neurons are capable of transmitting pruriceptive information from the cheek Giesler 2013, 2014b).…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…The intensity theory states that the very same primary afferents are capable of triggering of both pruritus and pain (reviewed in Ross, 2011;Tóth and Bíró, 2013;Tóth et al, 2014). This model is supported by the observations that 1) intradermal capsaicin injection can cause both itch and pain Klein et al, 2011;Sikand et al, 2011) in a dose-dependent manner, and 2) desensitization to topical capsaicin creams alleviates both pain and pruritus (see Szallasi and Blumberg, 1999). However, modern research points to the existence of an autonomous pruriceptive system (Fig.…”

GABAA Receptors in the Central Nucleus of the Amygdala Are Involved in Pain- and Itch-Related Responses

“…In the present study, therefore, we investigated the effects of GABA A receptor in the CeA on scratching behavior in 5-hydroxytryptamine-elicited acute itch and chronic dry skin itch, which appears to well discriminate between itch and pain elicited by chemical stimuli. 2,12 Methods Animals Adult male Sprague Dawley rats (250-320 g) were obtained from Chongqing Medical University Animal House Center and maintained at Children's Hospital of Chongqing Medical University Animal Care Centre. Animals were pair-housed in plastic cages in a temperature-controlled (21 C) colony room on a 12/12 hour light/dark cycle.…”