Anxiety-like behaviour in rats with mononeuropathy is reduced by the analgesic drugs morphine and gabapentin

Abstract

Anxiety has been described as an important comorbidity in patients suffering from chronic pain. However, in animals the connection between persistent pain and anxiety has hardly been investigated. Therefore, in the current study it was assessed whether chronic pain also causes anxiety-like behaviour in animals and if it can be reversed by analgesic or anxiolytic drugs. Neuropathic pain was induced in rats by partial sciatic nerve ligation (PNL) and chronic constriction injury (CCI). Mechanical hypersensitivity was assessed by the “electronic algometer”, while anxiety-like behaviour was measured by using the elevated plus maze. In both neuropathic pain models, rats exhibited mechanical hypersensitivity, whereas a significant increase in anxiety-like behaviour was observed only in CCI rats (time spent in open arms decreased significantly from 99 ± 15.8 s in sham animals to 33.4 ± 7.5 s in CCI animals). Furthermore, midazolam (0.5 mg/kg; i.p.) significantly reduced anxiety-like behaviour in both sham- and CCI-operated animals without influencing mechanical hypersensitivity. Morphine (3 mg/kg; i.p.) and gabapentin (30 mg/kg; i.p.) significantly attenuated anxiety-like behaviour in the CCI lesioned rats: morphine increased entries into open arms from 3.0 ± 0.4 to 7.7 ± 1.4 ( P = 0.01), gabapentin elevated this value from 4.7 ± 1 to 7.5 ± 0.9 ( P = 0.02). These data suggest that rats subjected to neuropathic pain models develop anxiety-like behaviour which can be reversed by appropriate analgesic treatment. Morphine and gabapentin had no anxiolytic-like effect in sham treated animals, thus their effect on anxiety-like behaviour in the neuropathic pain model is likely indirect via their anti-nociceptive properties.