Detection of cold allodynia is a very important aspect in the study of pain behavior. An effective and concise device for detecting cold pain has always been the hope of many researchers. Here, an easily produced and operated cold plate device is presented for the assessment of cold allodynia in mice. The device used to detect cold allodynia has two components: a chamber consists of a cylinder for animal experiment and a cube box around the chamber for holding ice to keep temperature stable. In the testing chamber, a mouse was placed on the circular plexiglass plate steady at 4 °C above ice for five minutes. The tested mouse will lift its paw when exposed to the cold plate. The number of lifts will present animal’s response to the degree of cold stimulation. To evaluate this approach, three commonly used pain models of mice were tested: formalin test, bone cancer pain (BCP), and chronic constriction injury (CCI). As is reported in other literatures, these three pain mice models showed increased sensitivity to cold stimulation. The new device is indeed suitable for detecting cold allodynia behavior in mice. Comparisons with existing devices of detecting cold allodynia, such as the cold plate in the market (UGO, Panlab, Columbus, etc.), the new device has the advantages of low cost, simple operation and easy popularization and can detect cold allodynia behavior of mice very well. This is a very practical and economical device to detect cold allodynia behavior.

Patients suffering from cancer induced bone pain (CIBP) have a poor quality of life that is exacerbated by the lack of effective therapeutic drugs. Monkshood is a flowering plant that has been used in traditional Chinese medicine where it has been used to relieve cold pain. Aconitine is the active component of monkshood, but the molecular mechanism for how this compound reduces pain is unclear. In this study, we employed molecular and behavioral experiments to explore the analgesic effect of aconitine. We observed aconitine alleviated cold hyperalgesia and AITC (allyl-isothiocyanate, TRPA1 agonist) induced pain. Interestingly, we found aconitine directly inhibits TRPA1 activity in calcium imaging studies. More importantly, we found aconitine alleviated cold and mechanical allodynia in CIBP mice. Both the activity and expression of TRPA1 in L4 and L5 DRG (Dorsal Root Ganglion) neurons were reduced with the treatment of aconitine in the CIBP model. Moreover, we observed aconiti radix (AR) and aconiti kusnezoffii radix (AKR), both components of monkshood that contain aconitine, alleviated cold hyperalgesia and AITC induced pain. Furthermore, both AR and AKR alleviated CIBP induced cold allodynia and mechanical allodynia. Taken together, aconitine alleviates both cold and mechanical allodynia in cancer induced bone pain via the regulation of TRPA1. This research on the analgesic effect of aconitine in cancer induced bone pain highlights a component of a traditional Chinese medicine may have clinical applications for pain.

Uterine contraction-induced pain (UCP) represents a common and severe form of visceral pain. Nerve fibers that innervate uterine tissue express the transient receptor potential vanilloid channel 1 (TRPV1), which has been shown to be involved in the perception of UCP. The phosphoinositide-interacting regulator of TRP (Pirt) may act as a regulatory subunit of TRPV1. The intraperitoneal injection of oxytocin into female mice after a 6-day priming treatment with estradiol benzoate induces writhing responses, which reflect the presence of UCP. Here, we first compared writhing response between Pirt^+/+ and Pirt^−/− mice. Second, we examined the innervation of Pirt-expressing nerves in the uterus of Pirt^−/− mice by immunofluorescence and two-photon microscopy. Third, we identified the soma of dorsal root ganglion (DRG) neurons that innerve the uterus using retrograde tracing and further characterized the neurochemical properties of these DRG neurons. Finally, we compared the calcium response of capsaicin between DRG neurons from Pirt^+/+ and Pirt^−/− mice. We found that the writhing responses were less intensive in Pirt^−/− mice than in Pirt^+/+ mice. We also observed Pirt-expressing nerve fibers in the myometrium of the uterus, and that retrograde-labeled cells were small-diameter, unmyelinated, and Pirt-positive DRG neurons. Additionally, we found that the number of capsaicin-responding neurons and the magnitude of evoked calcium response were markedly reduced in DRG neurons from Pirt^−/− mice. Taken together, we speculate that Pirt plays an important role in mice uterine contraction-induced pain.