A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats

Abstract

Background Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its anti-nociceptive properties. Methods We examined whether the spared nerve injury (SNI) model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats SNI-induced depression. Results SNI-treated rats, compared with control, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10mg/kg) did not alter SNI-induced hypersensitivity; however, it treated SNI-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control 5 days after administration). Conclusions Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain.

Small-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in Mice

“…Sustained antidepressant effects have been reported following ketamine administration in the TST and FST in mice although reports to date are equivocal (Autry et al, 2011;Bechtholt-Gompf et al, 2011;Koike et al, 2011;Maeng et al, 2008;Popik et al, 2008). Such a profile is consistent with other reports where acute administration with ketamine rapidly ameliorates anhedonic and anxiogenic behaviours in rats exposed to chronic unpredictable stress (Garcia et al, 2009;Li et al, 2011) and depressionrelated behaviour in a nerve injury model of neuropathic pain (Wang et al, 2011). It was therefore of interest to determine if compounds, which modulate the NMDA-R/ PSD-95/nNOS signalling pathway produce sustained actions similar to those obtained with IC87201.…”

Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain

“…Consistently, depressive-and anxiety-like behaviors have been observed in animal models of peripheral nerve injury, as indexed by the increase in total immobility time in the forced swimming or tail suspension tests (Gai et al, 2014;Jesse et al, 2010;Wang et al, 2011;Yalcin et al, 2011). Chronic pain-related affective impairments develop already 2 weeks after the SNI surgery (Norman et al, 2010;Palazzo et al, 2015;Suzuki et al, 2007), decreased motivation and anhedonia develop in mice at 7 days following nerve injury e remain stable up to 21 days (Schwartz et al, 2014).…”

“…Indeed, chronic maladaptive plasticity underlies emotional, affective and cognitive symptoms of neuropathic pain syndrome, i.e. anxiety, anhedonia and depression (Baliki et al, 2006;Neugebauer et al, 2009;Oluigbo et al, 2012;Wang et al, 2011;Yalcin et al, 2014).…”

AMPAkines Have Novel Analgesic Properties in Rat Models of Persistent Neuropathic and Inflammatory Pain

“…As described previously, 42 on the first session of the test, each animal was placed for fifteen minutes into a standard clear Porsolt chamber (Lafayette Instrument Company, Lafayette, IN) with water at 25° C filled to 25 cm. Afterwards, the animal was taken out of the chamber, dried and put back in its home cage.…”