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Background: Exercise is a known trigger of the inhibitory pain modulation system and its analgesic effect is termed exercise-induced hypoalgesia (EIH). Previous studies have demonstrated that rats with deficient analgesic response following exercise develop more significant hypersensitivity following nerve injury compared to rats with substantial analgesic response following exercise., Objectives: A rat model of EIH as an indicator of the pain inhibitory system's efficiency was used to explore the association between EIH profiles and the effect of pharmacotherapy on rat's neuropathic pain., Methods: EIH profiles were assessed by evaluating paw responses to mechanical stimuli before and after exercise on a rotating rod. Rats with a reduction of ≤33% in responses were classified as low EIH and those with ≥67% as high EIH. Low and high EIH rats underwent sciatic nerve chronic constriction injury (CCI). Paw responses to mechanical stimuli were measured at baseline, following CCI, and after treatment with diclofenac, duloxetine or pregabalin. In a different group of low and high EIH rats, EIH was measured before and following treatment with the same medications., Results: Low EIH rats developed more significant hypersensitivity following CCI. Duloxetine and pregabalin successfully reduced hypersensitivity, although significantly more so in low EIH rats. Diclofenac had limited effects, and only on low EIH rats. Four days of duloxetine administration transformed low EIH rats' profiles to high EIH., Conclusions: The findings of this study suggest that EIH profiles in rats can not only predict the development of hypersensitivity following injury but may also support targeted pharmacological treatment., Significance: Exercise is a known trigger of the inhibitory pain modulation. Rats with deficient analgesic response following exercise develop more significant hypersensitivity following nerve injury. Pain modulation profiles in rats can also support targeted pharmacological treatment; rats with deficient analgesic response following exercise benefit more from treatment with duloxetine and gabapentin. Treatment with duloxetine can improve pain modulation profile., (© 2022 European Pain Federation - EFIC ®.)

Background: Approximately 40% of patients with chronic low back pain have a neuropathic component. In this study, we assessed the effects of analgesics on tactile hypersensitivity and walking distance in the rat cauda equina compression (CEC) model of neuropathic low back pain., Methods: The effects of analgesics on tactile hypersensitivity were examined using the von Frey test in CEC and partial sciatic nerve ligation (pSNL) models. Effects on walking distance were assessed using a treadmill test. Levels of α2δ1 subunit and ATF-3 mRNA in dorsal-root ganglion (DRG) neurons and those of α2δ1 subunit protein in the spinal cord were determined using quantitative RT-PCR and western blotting, respectively. Histological features were assessed using immunohistological methods., Results: Histological changes indicating nerve damage (increase in ATF-3 mRNA, decrease in NF-200 and an increase in CD68 immunoreactivity) were observed in the CEC model. Duloxetine had analgesic effects in both models and improved walking distance in the CEC model. Pregabalin had analgesic effects in both models; however, the effect was weaker in the CEC model than in the pSNL model. α2δ1 subunit expression in DRG neurons and in the spinal cord was unchanged in the CEC model, but significantly increased in the pSNL model. Indomethacin had no analgesic effect in either model. Intrathecal yohimbine inhibited the effects of duloxetine with significant effects on depression., Conclusions: These findings suggest that the analgesic effects of duloxetine are mainly mediated by the spinal monoamine system, independent of the antidepressant effects of this agent., Significance: The findings of this study suggest that duloxetine may be an effective treatment of broad neuropathic pain states, including neuropathic low back pain. The analgesic effects of duloxetine might be mediated by alterations of the descending pain modulatory pathways in the spinal cord, independent of the antidepressant effects., (© 2017 European Pain Federation - EFIC®.)

Background: Hind paw injection of complete Freund's adjuvant (CFA) is a commonly used sub-acute inflammatory pain model in rodents with typical subjective endpoint measurements of paw withdrawal to thermal or mechanical stimuli., Methods: Here, we assessed CFA-induced reduction of exploratory activity in a novel environment (CRANE) as an objective nociceptive endpoint in rats. CFA (50%) was subcutaneously injected into the plantar aspect of the hind paw either unilaterally or bilaterally (150 μL/paw). Exploratory activity was recorded using an automated locomotor activity system., Results: Bilateral CFA injection reduced exploratory activity 4-48 h following injection, compared to sham controls. Unilateral CFA injection produced less reduction of exploratory activity, compared to bilateral injection. Effects of orally dosed standard analgesics on CRANE were examined 48 h following bilateral CFA injection. Diclofenac treatment produced dose-related reversal of CRANE at 0.03-1.0 mg/kg with a plateau effect observed at higher doses (up to 30 mg/kg). Ibuprofen also produced dose-related reversal CRANE at 0.3-3.0 mg/kg with a plateau effect at higher doses (up to 60 mg/kg). Similarly, celecoxib produced dose-related reversal CRANE at 3-10 mg/kg, but not 30 mg/kg. Gabapentin (up to 100 mg/kg) and duloxetine (up to 30 mg/kg) produced no reversal of CRANE., Conclusions: The results presented here demonstrate that CRANE provides an objective assessment of pain behaviours for sub-acute inflammatory pain in rats. The pharmacological profile of standard analgesics supports that CRANE model may potentially be used to identify novel analgesic agents for the treatment of sub-acute inflammatory pain., (© 2015 European Pain Federation - EFIC®)