Reduced behavioral withdrawal responses during fear retrieval in adult mice and rats

Abstract

Pain triggers emotional changes in humans and animals, including fear and anxiety. Conversely, fear and anxiety may enhance suffering of patients with pain. However, in animal models of acute pain, it has been reported that fear may inhibit pain by activating endogenous inhibitory systems. In this study, we wanted to examine if behavioral withdrawal responses may be affected during fear retrieval, a condition where fear-associated tone is applied. We found that thermal pain thresholds were significantly increased during fear retrieval. Our results indicate that animals are suffering fear like-events, while their behavioral responses are inhibited. These results indicate that it will be important to evaluate both emotional and behavioral withdrawal responses for future development of new pain medicine.

Keywords: Fear; mice; pain threshold; rats.

Figure 1.

Reduced behavioral withdrawal responses to noxious heat during fear retrieval in mice and rats. (a) Schematic diagram showing the different fear conditioning models preformed on five rodent groups. Experiment group rodents were exposed to a context with tone/shock pairing. The tone was 96 dB with 2.2 kHz for 30 s. The foot shock (0.75 mA for mice, 2.0 mA for rats) lasted for 2 s. The withdrawal latency to radiant heat was measured after foot shock after 6 h or 24 h with tone pairing. For naive group, rodents were just exposed to a context, and the withdrawal latency was measured without a tone after 6 h. For tone group, rodents were exposed to a context with a tone alone, and the withdrawal latency was measured with a tone after 6 h. For shock group, rodents were exposed to a context with tone/shock pairing, and the withdrawal latency was measured without a tone after 6 h. (b) The withdrawal latency was increased significantly in after 6-h group compared with control groups in mice. n = 12 for after 6-h group (eight male and four female mice), n = 8 for each control group (four male and four female mice), **p < 0.01, N.S. not significant. There was no difference in control groups. (c) The withdrawal latency was decreased in after 24-h group compared with 6 h after fear conditioning in mice. n = 12 for after 24-h groups (eight male and four female mice), **p < 0.01, N.S. not significant. The values of after 6-h group in (c) are totally the same with (b). (d) The withdrawal latency was increased significantly in after 6-h group compared with control groups in rats. n = 12 for after 6-h group (eight male and four female rats), n = 8 for each control group (four male and four female rats), **p < 0.01, N.S. not significant. There was no difference in control groups. (e) The withdrawal latency was decreased in after 24-h group compared with 6-h after fear conditioning in rats. n = 8 for after 24-h group (four male and four female mice), *p < 0.05, N.S. not significant. The values of after 6-h group in (e) are totally the same with (d).