Depression and anxiety are common comorbidities of
neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked
pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of
tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats. We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of
neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors. In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to
sham (P<0.001).
Tramadol increased the PWT by 336% in CCI rats (P<0.001) and by 16% in
sham (P<0.05). On the EPM, CCI rats spent 45% less time than
sham on the open arms of the maze (P<0.05).
Tramadol increased the time spent on the open arms of CCI rats by 67% (P<0.05) and had no significant effect on
sham. During the FST, CCI rats showed 28% longer immobility than
sham (P<0.01).
Tramadol reduced the immobility time in CCI rats by 22% (P<0.001), while having no effect on
sham.
Tramadol reversed the changes in mechanical sensitivity as well as anxiety-related and depression-associated behaviors that are caused by injury of the sciatic nerve with only minor effects in the absence of injury. These data suggest that
tramadol relieves
chronic pain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP.