The differential effects of depression on evoked and spontaneous pain behaviors in olfactory bulbectomized rats

Abstract

Although it has been accepted that depression and pain are common comorbidities, their interaction is not fully understood. The current study was aimed to investigate the effects of depression on both evoked pain behavior (thermal-induced nociception) and spontaneous pain behavior (formalin pain) using an olfactory bulbectomy (OB) rat model of depression. Emotional behaviors were assessed by open field and Morris water maze tests. The results showed that the depressed rats exhibited stronger tolerance to noxious thermal stimulation compared to non-depressed animals. In contrast, the spontaneous nociceptive behaviors induced by formalin injection were significantly enhanced in the OB rats in comparison to control rats. These results demonstrated that depression can have differential effects on stimulus-evoked pain and spontaneous pain, with alleviation in the former while aggravation in the latter. The present study has confirmed our previous findings that depression can inhibit evoked pain but facilitate spontaneous pain, and provides evidence that the OB depression model is a feasible model for studying the relationship between depression and pain.

Fig.1

Schematic diagram of the experimental protocol. Rats were divided into two groups (OB and SHAM groups, receiving olfactory bulbectomy or sham surgery, respectively) based on the results of the open-field test. Both groups were further divided into two sub-groups for either radiant heat (RH) or Formalin test, i.e., OB/RH, OB/Formalin, SHAM/RH, and SHAM/Formalin groups. Baseline thermal thresholds were measured in the OB/RH and SHAM/RH rats. Then all animals were tested in the open field and Morris water maze. Evoked pain was assessed by the paw withdrawal latency (PWL) induced by heat stimulation. Spontaneous pain was evaluated by the nocifensive paw-licking behavior following formalin injection. OF: open field; MWM: Morris water maze.

Fig.2

Behavioral outcome of the OB model for depression. (A) Body weights. The body weights of rats showed significant decrease in the OB group in comparison to the control group over the 14-day post-operation period. (B-C) Open field test. Significant higher level of locomotor activity and rearing behaviors were found in the OB rats than in the control rats. (D-E) Morris water maze training. In four training days, rats exhibited significant more activity and longer time to explore the platform in the OB rats than in the control group. (F) Morris water maze test. The percentage of time spent in the quadrant II where the platform was located was significantly lower in the OB group than in the SHAM group. Data are presented as mean ± SEM (n = 20-24). ** P < 0.01; *** P < 0.001.

Fig.3

Influence of depression on pain behaviors. (A) Evoked pain by thermal stimulation. Rats displayed significantly longer PWL to noxious heat stimuli in OB group than in SHAM group, suggesting a reduction of the thermal evoked pain in the depressive state (n = 10-11). (B-E) Spontaneous pain by formalin injection. Rats in the OB group exhibited significantly increased licking behaviors in the early and late phases as well as in the interphase following formalin injection, indicating that OB surgery resulted in an enhancement of the spontaneous ongoing pain (n =10-13). Data are presented as mean ± SEM. * P < 0.05; ** P < 0.01; *** P < 0.001, compared with their respective control group.