Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats

Cancer-associated pain is debilitating. However, the mechanism underlying cancer-induced spontaneous pain and evoked pain remains unclear. Here, using behavioral tests with immunofluorescent staining, overexpression, and knockdown of TRESK methods, we found an extensive distribution of TRESK potassium channel on both CGRP+ and IB4+ nerve fibers in the hindpaw skin, on CGRP+ nerve fibers in the tibial periosteum which lacks IB4+ fibers innervation, and on CGRP+ and IB4+ dorsal root ganglion (DRG) neurons in rats. Moreover, we found a decreased expression of TRESK in the corresponding nerve fibers within the hindpaw skin, the tibial periosteum and the DRG neurons in bone cancer rats. Overexpression of TRESK in DRG neurons attenuated both cancer-induced spontaneous pain (partly reflect skeletal pain) and evoked pain (reflect cutaneous pain) in tumor-bearing rats, in which the relief of evoked pain is time delayed than spontaneous pain. In contrast, knockdown of TRESK in DRG neurons produced both spontaneous pain and evoked pain in naïve rats. These results suggested that the differential distribution and decreased expression of TRESK in the periosteum and skin, which is attributed to the lack of IB4+ fibers innervation within the periosteum of the tibia, probably contribute to the behavioral divergence of cancer-induced spontaneous pain and evoked pain in bone cancer rats. Thus, the assessment of spontaneous pain and evoked pain should be accomplished simultaneously when evaluating the effect of some novel analgesics in animal models. Also, this study provides solid evidence for the role of peripheral TRESK in both cancer-induced spontaneous pain and evoked cutaneous pain.

A Comparative Neuro-Histological Assessment of Gluteal Skin Thickness and Cutaneous Nociceptor Distribution in Horses and Humans

The current project aims to build on knowledge of the nociceptive capability of equine skin to detect superficial acute pain, particularly in comparison to human skin. Post-mortem samples of gluteal skin were taken from men (n = 5) and women (n = 5), thoroughbreds and thoroughbred types (mares, n = 11; geldings, n = 9). Only sections that contained epidermis and dermis through to the hypodermis were analysed. Epidermal depth, dermal depth and epidermal nerve counts were conducted by a veterinary pathologist. The results revealed no significant difference between the epidermal nerve counts of humans and horses (t = 0.051, p = 0.960). There were no significant differences between epidermal thickness of humans (26.8 µm) and horses (31.6 µm) for reference (left side) samples (t = 0.117, p = 0.908). The human dermis was significantly thinner than the horse dermis (t = −2.946, p = 0.007). Epidermal samples were thicker on the right than on the left, but only significantly so for horses (t = 2.291, p = 0.023), not for humans (t = 0.694, p = 0.489). The thicker collagenous dermis of horse skin may afford some resilience versus external mechanical trauma, though as this is below the pain-detecting nerve endings, it is not considered protective from external cutaneous pain. The superficial pain-sensitive epidermal layer of horse skin is as richly innervated and is of equivalent thickness as human skin, demonstrating that humans and horses have the equivalent basic anatomic structures to detect cutaneous pain. This finding challenges assumptions about the physical capacity of horses to feel pain particularly in comparison to humans, and presents physical evidence to inform the discussion and debate regarding the ethics of whipping horses.

An atypical case of pyoderma gangrenosum in a dog

Neutrophilic and ulcerative dermatitis is reported in a mixed breed dog. The condition was considered to be an atypical case of pyoderma gangrenosum. Clinically, it had a more superficial ulceration, a more pronounced pustular component and lacked the characteristic cutaneous pain and tenderness of the lesions. The diagnosis of pyoderma gangrenosum was made as a diagnosis of exclusion. The dog showed an excellent response to treatment with ciclosporin (Cyclavance, Virbac, Leuven, Belgium).

Different processing of meningeal and cutaneous pain information in the spinal trigeminal nucleus caudalis

Introduction Within superficial trigeminal nucleus caudalis (Sp5C) (laminae I/II), meningeal primary afferents project exclusively to lamina I, whereas nociceptive cutaneous ones distribute in both lamina I and outer lamina II. Whether such a relative absence of meningeal inputs to lamina II represents a fundamental difference from cutaneous pathways in the central processing of sensory information is still unknown. Methods We recorded extracellular field potentials in the superficial Sp5C of anesthetised rats evoked by electrically stimulating the dura mater, to selectively assess the synaptic transmission between meningeal primary afferents and second-order Sp5C neurons, the first synapse in trigeminovascular pathways. We tested the effect of systemic morphine and local glycinergic and GABAAergic disinhibition. Results Meningeal stimulation evokes two negative field potentials in superficial Sp5C. The conduction velocities of the activated primary afferents are within the Aδ- and C-fibre ranges. Systemic morphine specifically suppresses meningeal C-fibre-evoked field potentials, and this effect is reversed by systemic naloxone. Segmental glycinergic or GABAAergic disinhibition strongly potentiates meningeal C-fibre-evoked field potentials but not Aδ-fibre ones. Interestingly, the same segmental disinhibition conversely potentiates cutaneous Aδ-fibre-evoked field potentials and suppresses C-fibre ones. Conclusion These findings reveal that the different anatomical organization of meningeal and cutaneous inputs into superficial Sp5C is associated with a different central processing of meningeal and cutaneous pain information within Sp5C. Moreover, they suggest that the potentiation upon local disinhibition of the first synapse in trigeminovascular pathways may contribute to the generation of headache pain.