Therapeutic effects of diclofenac, pregabalin, and duloxetine on disuse-induced chronic musculoskeletal pain in rats

The aim of this study was to clarify the mechanism of disuse-induced muscle hyperalgesia through the evaluation of the pharmacological behaviour of muscle hyperalgesia profiles in chronic post-cast pain (CPCP) rats with acute and chronic-phase mirror-image muscle hyperalgesia treated with diclofenac (NSAID), pregabalin (an inhibitor of Ca(2+) channel α2δ), and duloxetine (SNRI). After 2 weeks of cast immobilization, the peak cross-sectional area and muscle wet weight of the ipsilateral soleus and gastrocnemius muscles decreased more significantly in CPCP rats than in untreated rats. Histological findings revealed disuse-induced muscle atrophy in CPCP rats. The blood biochemical parameters of CPCP rats in acute and chronic phases did not differ significantly from those of untreated rats. The diclofenac and pregabalin-treated groups exhibited no improvement in acute or chronic muscle hyperalgesia. In contrast, the duloxetine-treated group exhibited an improvement in acute muscle hyperalgesia, but showed no apparent effect on chronic muscle hyperalgesia on ipsilateral or contralateral sides. However, the chronic muscle hyperalgesia was reversed by intrathecal administration of DAMGO (a μ-opioid receptor agonist). The results suggest that chronic muscle hyperalgesia in CPCP rats did not result from an inflammatory mechanism, and there is only a low probability that it’s caused by a neuropathic mechanism.