Inhibitory effect of lidocaine on pain and itch using formalin-induced nociception and 5′-guanidinonaltrindole-induced scratching models in mice: Behavioral and neuroanatomical evidence

Abstract

The aim of this study was to establish the effect of lidocaine, a local anesthetic, on pain and itch using formalin-induced nociception and kappa opioid antagonist-induced scratching models in mice. We investigated if local intradermal pretreatment (at −10 min) with lidocaine N-ethyl bromide (lidocaine, 2%, 0.1 ml) antagonizes behavioral responses and prevents c-fos expression induced by pain and itch. Male, Swiss Webster mice (25-30 g, n=6-10) were used. Formalin (5%, 20 µl, s.c.) or saline was administered to the right dorsal hindpaw and the time spent licking this paw was recorded at 0-10 min and 20-35 min. For itching, mice were challenged with 5′-guanidinonaltrindole (GNTI, 0.3 mg/kg, s.c., behind the neck) or saline and the number of neck-directed scratches with hindpaws was counted for 30 min. C-fos immunohistochemistry was performed in lumbar (for pain) and cervical (for scratching) spinal sections 2 h after respective treatments. We found that lidocaine (a) antagonizes both formalin-induced pain and GNTI-induced scratching and (b) prevents c-fos expression evoked by pain (medial side of the superficial layer and deeper layers of the dorsal horn) and itch (lateral side of the superficial layer of the dorsal horn). Additionally, GNTI caused c-fos activation in mice wearing an Elizabethan collar (to prevent scratching of the neck) suggesting that GNTI provokes c-fos expression by inducing an itch sensation. Our results highlight the antipruritic properties of lidocaine and argue for its comprehensive clinical testing against pruritic states.

Investigation of the role of βarrestin2 in kappa opioid receptor modulation in a mouse model of pruritus

“…NorBNI was first described as a pruritogen in ICR mice (Kamei and Nagase, 2001), whereas a majority of 5′GNTI-induced pruritus has been characterized in Swiss-Webster mice (Inan et al, 2009a, b, 2011). Different strains of mice can inherently have different phenotypes that present when challenged with a pruritogen.…”

“…Conversely, KOR antagonists such as nor-binaltorphimine (NorBNI) and 5′guanadinonaltrindole (5′GNTI) induce acute pruritus (Inan t al., 2009a, b; Kamei and Nagase, 2001). Since the antagonists can induce itch it is attractive to speculate that the underlying tone of the endogenous KOR agonists, dynorphins, naturally suppress the itch response.…”

Toll-like receptor 4 contributes to chronic itch, alloknesis, and spinal astrocyte activation in male mice

“…The spontaneous scratching was video recorded for 1 hour on day 6 and total number of scratches was counted blindly. As previously reported [23], we let mouse wear an Elizabethan Collar on the neck to prevent mouse from scratching the cheek skin so that we can test the effect of scratching on AEW-induced spinal cord astrogliosis.…”

Management of Itch in Atopic Dermatitis

“…Of note, a recent study on scratch behavior in mice does point to a strong inhibitory effect of lidocaine on itch. 229 This and the few existing case reports on the alleviating effect of lidocaine on neuropathic itch lead us to hypothesize that lidocaine might be beneficial for patients with AD. To prove this hypothesis, further basic research and controlled studies are needed to evaluate the safety and efficacy of lidocaine in the treatment of pruritus in AD.…”