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. 2015 Mar 30:591:207-211.
doi: 10.1016/j.neulet.2015.01.066. Epub 2015 Jan 28.

Neonatal handling (resilience) attenuates water-avoidance stress induced enhancement of chronic mechanical hyperalgesia in the rat

Pedro Alvarez  1 , Jon D Levine  2 , Paul G Green  1
Affiliations

Neonatal handling (resilience) attenuates water-avoidance stress induced enhancement of chronic mechanical hyperalgesia in the rat

Pedro Alvarez et al. Neurosci Lett. .

Abstract

Chronic stress is well known to exacerbate pain. We tested the hypothesis that neonatal handling, which induces resilience to the negative impact of stress by increasing the quality and quantity of maternal care, attenuates the mechanical hyperalgesia produced by water-avoidance stress in the adult rat. Neonatal male rats underwent the handling protocol on postnatal days 2-9, weaned at 21 days and tested for muscle mechanical nociceptive threshold at postnatal days 50-75. Decrease in mechanical nociceptive threshold in skeletal muscle in adult rats, produced by exposure to water-avoidance stress, was significantly attenuated by neonatal handling. Neonatal handling also attenuated the mechanical hyperalgesia produced by intramuscular administration of the pronociceptive inflammatory mediator, prostaglandin E2 in rats exposed as adults to water-avoidance stress. Neonatal handling, which induces a smaller corticosterone response in adult rats exposed to a stressor as well as changes in central nervous system neurotransmitter systems, attenuates mechanical hyperalgesia produced by water-avoidance stress and enhanced prostaglandin hyperalgesia in adult animals.

Keywords: Housing density; Muscle hyperalgesia; Neonatal handling; Resilience; Stress.

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Conflict of interest statement

Disclosures

The authors have no conflicts of interest.

Figures

Figure 1
Figure 1. Neonatal handling attenuates stress-induced muscle hyperalgesia in adult rats
Water-avoidance stress produces a significant decrease in nociceptive threshold in the gastrocnemius muscle (3 d after the last exposure to the stressor). Water-avoidance stress induces reduction in nociceptive threshold that is markedly attenuated in neonatally handled rats. *p<0.05.
Figure 2
Figure 2. Enhancement of prostaglandin E2 (PGE2) hyperalgesia by water-avoidance stress is attenuated in neonatally handled rats
Mechanical hyperalgesia in the gastrocnemius muscle was measured 1, 4, 24 and 72 h after intramuscular administration of PGE2, in naive non-stressed, neonatally handled non-stressed, water-avoidance stressed rats, and water-avoidance stressed rats that were neonatal handled. In naive non-stressed rats and in neonatally handled non-stressed rats, PGE2-induced a decrease in mechanical nociception present 1 hour post-injection, that returns to near baseline at the 4-h time point. In water-avoidance stressed rats, the decrease in nociceptive threshold induced by PGE2, administered 1 day after the last stress, remained largely undiminished 72 h post-PGE2 administration, and was significantly different from a non-stressed control group of rats (#P<0.0001, 2-way repeated measures ANOVA). In neonatally handled rats, the decrease in nociceptive threshold produced by exposure to water-avoidance stress is significantly attenuated compared to the non-handled stress group, at the 4-, 12- and 72-h time points (*P<0.0001, 2-way repeated measures ANOVA).
Figure 3
Figure 3. Housing density is a factor in attenuation of water-avoidance stress-induced muscle hyperalgesia by neonatal handling
Water-avoidance stress-induces muscle hyperalgesia that is completely eliminated in 3 rats per cage housed rats, while 2 rats per cage housed neonatally handled rats show a significant attenuation of muscle hyperalgesia (F2,59 = 110.1, P<0.001, 2-way repeated measures ANOVA). * p<0.05.
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