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. 2011 Jun 30:185:166-73.
doi: 10.1016/j.neuroscience.2011.04.020. Epub 2011 Apr 15.

Stress enhances muscle nociceptor activity in the rat

Affiliations

Stress enhances muscle nociceptor activity in the rat

X Chen et al. Neuroscience. .

Abstract

Chronic widespread pain, such as observed in irritable bowel (IBS) and fibromyalgia (FMS) syndrome, are markedly affected by stress. While such forms of stress-induced hyperalgesia are generally considered manifestations of "central sensitization," recent studies in patients with IBS and FMS suggest an additional, peripheral contribution. To examine the effect of stress on muscle nociceptor function, we evaluated activity in nociceptors innervating the gastrocnemius muscle in an animal model of chronic widespread pain, water avoidance stress, in the rat. This stressor, which produces mechanical hyperalgesia in skeletal muscle produced a significant decrease (∼34%) in mechanical threshold of muscle nociceptors and a marked, ∼two-fold increase in the number of action potentials produced by a prolonged (60 s) fixed intensity suprathreshold 10 g stimulus. Stress also induced an increase in conduction velocity from 1.25 m/s to 2.09 m/s, and increased variability in neuronal activity. Given that these changes, each of at least moderate magnitude, would be expected to enhance nociceptor activity, it is likely that, taken together, they contribute to the enhanced nociception observed in this model of stress-induced chronic widespread pain.

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Figures

Figure 1
Figure 1
A. Mechanical threshold of nociceptors innervating the gastrocnemius muscle, from water-avoidance stress-exposed (n = 26) and control rats (n = 40). Muscle nociceptors in water-avoidance-exposed rats had significantly lower mechanical thresholds than nociceptors from naïve control rats (P<0.05, Welch’s correction for the Student’s t-test). B. Scattergram of mechanical thresholds of individual muscle nociceptors from naïve control and water-avoidance stress-exposed rats.
Figure 2
Figure 2
The response of nociceptors to sustained (60 s) suprathreshold (10 g) von Frey hair mechanical stimuli in muscle nociceptors. Mean values (A) and individual fibers (B) are shown from naïve control and water-avoidance stress-exposed rats. The responses of the nociceptors from the water-avoidance group (n = 26) were significantly higher (for 0-10s and 0-60s) than those of control rats (n = 40, *P<0.05, Welch’s correction for the Student’s t-test). (C) Single-unit C-fiber recordings of action potentials evoked by a 10-g stimulus in naïve control and in water-avoidance stressed rats.
Figure 3
Figure 3
The time course of the average responses of nociceptors during the 60 s suprathreshold stimulus, for naïve control (n = 40) and water-avoidance stressed (n = 26) rats; bin width 1 s. The number of action potentials in muscle afferents from stressed rats was significantly greater during the first 1 – 8 s stimulus period (two-way repeated measures ANOVA, with Bonferroni post hoc test; † P
Figure 4
Figure 4
The inter-stimulus interval (ISI) distribution of muscle nociceptors in response to sustained (60 s) suprathreshold (10 g) von Frey hair mechanical stimuli, for water-avoidance stress-exposed (n = 26) and naïve control (n = 40) rats (bin width 1 s).
Figure 5
Figure 5
A. Mean conduction velocities from water-stressed rats (2.09 ± 0.3 n=26) were significantly greater than from naïve rats (1.25 ± 0.11 n=40, Welch’s correction for the Student’s t-test, p < 0.05). B. Scattergram of conduction velocities of muscle nociceptors in naïve control and water-avoidance-treated rats.
Figure 6
Figure 6
The coefficient of variation (CV2) distribution of muscle nociceptors from water-avoidance stress-exposed (n = 26) and naïve control (n = 40) rats, in response to sustained (60 s) suprathreshold (10 g) von Frey hair mechanical stimulation. CV2 is significantly greater in neurons of rats exposed to water-avoidance stress, compared to naïve controls (two-way repeated measures ANOVA, P

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