Blocking of cytokines signalling attenuates evoked and spontaneous neuropathic pain behaviours in the paclitaxel rat model of chemotherapy‐induced neuropathy

Abstract

This study demonstrates that paclitaxel-treated rats exhibit, in addition to indices of mechanical and cold hypersensitivity, a behavioural sign of spontaneous pain, the principal compliant of patients with neuropathic pain. This was accompanied by upregulation in plasma levels of key cytokines/chemokines (IL-1α, IL-1β, IL-6, TNF-α, INF-γ and MCP-1) 31 days post-treatment. However, it is noteworthy that cytokine release, rather than nerve injury per se, may be causative of NP in this model of CIPNP. Nevertheless, our findings that pharmacological blockade of TNF-α, IL-1β and MCP-1 attenuated both evoked and spontaneous pain suggest that strategies that target inhibition of these cytokines may be effective in treating CIPNP.

Activation of Kv7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy

“…The test was repeated 35 d post STZ to determine whether the rats developed mechanical hypersensitivity. As reported previously [27][28][29] mechanical hypersensitivity was indicated by a significant decrease in the mean PWT. To determine effects of drugs on mechanical hypersensitivity, the test was also conducted at different time points after treatment with various drugs or their vehicles.…”

“…Pain behavioural testing was conducted on 64 rats by an experimenter who was blind to the various treatment groups of the animals. As we have reported previously [26][27][28], testing was performed in plastic chambers after the rats were acclimatised for 3 consecutive days to the procedure room, the testing chambers and the devices used (see below). On the testing days, the rats were also habituated to the chambers by placing each rat in the plastic chamber for at least 15 min before testing.…”

“…Behavioural testing for mechanical hypersensitivity (allodynia) Behavioural testing for mechanical hypersensitivity/allodynia was performed using an automated von Frey type system known as a dynamic plantar aesthesiometer touch stimulator (Ugo Basile, Italy) as described previously [28]. Briefly, rats were placed in plexiglass boxes (15 Â 15 Â 20 cm) on a wire mesh, and the midplantar surface of the left hind paw of each rat was stimulated with a blunt metal probe (0.5 mm in diameter) three times with a minimum of 5-min interval between each trial.…”

“…Behavioural testing for heat hypersensitivity/hyperalgesia was performed using Hargreaves analgesiometer (Ugo Basile, Comerio, Italy) as described previously [27][28][29]. Heat hypersensitivity was indicated by a significant decrease in the mean paw withdrawal latency (PWL) to a noxious heat stimulus applied to the midplantar surface of the hind paw (L4 dermatome) of each rat.…”

“…Before conducting the cold sensitivity test, rats were allowed to acclimate to the testing apparatus for $1 h, then the test was conducted by placing each rat on a metal surface of the cold plate maintained at 5 C within a transparent plexiglass chamber (16 Â 16 Â 27 cm). As described previously by various investigators [28,30], the duration (in seconds) of the escape/nocifensive behaviour (licking, lifting, guarding, shaking or biting of the hind paw or jumping) per a 2 min period was measured, using a stop watch, in control (vehicle treated) and STZ-treated rats. To determine the baseline values of cold sensitivity, rats were tested one day before STZ injection.…”