Progesterone reduces the expression of spinal cyclooxygenase‐2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain

Abstract

Our results suggest that progesterone, by modulating early neuroinflammatory events triggered after SCI, may represent a useful strategy to prevent the development of central chronic pain.

Anti‐allodynic and anti‐inflammatory effects of 17α‐hydroxyprogesterone caproate in oxaliplatin‐induced peripheral neuropathy

“…On the contrary, well known are the anti‐allodynic effects exerted by PR and its reduced metabolite allopregnanolone, neuroactive steroids with proven neuroprotective and anti‐inflammatory actions, in different animal models of neuropathic pain . In particular, we have recently shown that early and sustained PR administration to animals with a sciatic nerve chronic constriction injury or a spinal cord hemisection is able to avoid maladaptive changes leading to central sensitization, thus preventing the development of mechanical and thermal allodynia …”

“…Rats were placed on individual acrylic testing chambers (8 × 8 × 18 cm) upon an elevated metal grid and allowed to habituate to the environment for 15 minutes before testing. The animals were tested before initiating OXA administration in order to obtain normal baseline values and at different time points, twice per week, thereafter and until the designated end‐point, as previously described . Only rats showing normal responses to mechanical and thermal stimulation before chemotherapy were included in the experiments (n = 12 in each experimental group).…”

“…As previously reported, paw mechanical sensitivity was assessed by evaluating the response to normally innocuous mechanical stimuli using a series of eight calibrated von Frey filaments (1, 2, 4, 6, 8, 10, 15, 26 g; Stoelting, Wood Dale, Illinois). Each hair was delivered to the central plantar area of each hindpaw, and at least six measurements were made, following the “up‐and‐down” method described by Dixon and Chaplan et al A robust and immediate paw withdrawal together with a nocifensive behavior such as repetitive shaking or licking of the paw, intention to either attack the stimulus or escape was considered a positive response.…”

“…Seven days after initiating OXA/saline administration, OXA, OXA + HPGCp, and CTL animals (n = 8 in each experimental group) were killed by decapitation after being deeply anesthetized with ketamine/xilazine (90/10 mg/kg, ip). Bilateral lumbar DRG (L3‐L5) and spinal L4‐L5 segments were immediately removed, and the dorsal spinal halves were dissected by cutting through the central canal . Tissues were frozen and stored at −70°C until further studies were performed.…”

“…Data shown in Figures and correspond to the mean ± SEM of mRNA levels relative to control values (CTL animals). Statistical analysis was performed by applying one‐way analysis of variance ( anova ) and Neuman‐Keuls multiple comparison post‐test …”