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. 2011 Jul;12(7):811-8.
doi: 10.1016/j.jpain.2011.01.006. Epub 2011 Apr 9.

Further validation of a model of fibromyalgia syndrome in the rat

Paul G Green  1 , Pedro Alvarez, Robert W Gear, Dennis Mendoza, Jon D Levine
Affiliations

Further validation of a model of fibromyalgia syndrome in the rat

Paul G Green et al. J Pain. 2011 Jul.

Abstract

We have recently developed an animal model of fibromyalgia syndrome in the rat. In this model, rats exposed to unpredictable sound stress develop a delayed onset enhancement and prolongation of cytokine-induced mechanical hyperalgesia in muscle and skin. In this study, we tested the hypothesis that our model also manifests symptoms of common comorbid diagnoses: irritable bowel syndrome, temporomandibular disorder, and anxiety. Both visceral sensitivity and cytokine hyperalgesia in masseter muscle were present in the stressed rats. Furthermore, in an established model of irritable bowel syndrome-water avoidance-we observed significant muscle hyperalgesia. Finally, using the elevated plus maze to assess for anxiety level, we observed a significantly higher anxiety level in sound stress-exposed rats. Thus, unpredictable sound stress produces a condition in the rat with several features-delayed onset visceral and temporomandibular hyperalgesia and increased anxiety, as well as cutaneous and muscle hyperalgesia-commonly found in patients with fibromyalgia syndrome.

Perspective: A stress model-unpredictable sound-in the rat exhibits several features (cutaneous, musculoskeletal, and visceral hyperalgesia, as well as anxiety) that are found in patients with fibromyalgia syndrome. Thus, this model may be used to test hypotheses about the underlying mechanisms and response to therapy in patients with fibromyalgia.

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Figures

Figure 1
Figure 1. Sound stress increases visceromotor response
Rats were exposed to unpredictable sound stress and visceromotor responses were determined in the colorectal distension model, 1 or 14 d later. Compared to naïve (non-stressed) rats (open circles, n=15), the visceromotor response was significantly greater 14 (filled circles, n=9), but not 1 d after the last exposure to sound stress (filled squares, n=9).
Figure 2
Figure 2. Sound stress increases PGE2 hyperalgesia in masseter muscle
Administration of PGE2 (1 μg in 20 μl) produced a marked decrease in mechanical nociceptive threshold in the masseter muscle 1 h post-injection that returns to near baseline in control (non-stressed) rats (n=8), when tested 4 h post-injection. A similar PGE2 hyperalgesia was present in rats 1 d after the last session of chronic unpredictable sound stress (n=6). In contrast, 14 d after sound stress (n=8), PGE2 hyperalgesia was still near maximal 4 h post-injection (P<0.001). Inset figure shows that exposure to sound stress had little effect on nociceptive threshold (6.8% increase).
Figure 3
Figure 3. Sound stress increases anxiety-like behavior
Rats were exposed to unpredictable sound stress and anxiety-like behavior was evaluated using the elevated plus maze, 1 and 14 d later. Compared to pre-stress, rats had a significantly lower open arm/total entries (i.e. both arms combined) score 14 d, but not 1 d, after stress, which indicates an increased anxiety.
Figure 4
Figure 4. Water-avoidance stress increases PGE2 hyperalgesia in gastrocnemius muscle
Mechanical hyperalgesia in the gastrocnemius muscle was measured 1 and 4 h after intramuscular administration of PGE2, in control (non-stressed) water-avoidance protocol exposed rats. In control, non-stressed rats, PGE2–induced decrease in mechanical nociception was present 1 h post injection, but had returned to near baseline at the 4 h time point. A similar PGE2 hyperalgesia was present in rats 1 d or 14 d after the last session of water avoidance stress (n=12). In water-avoidance stressed rats, the decrease in nociceptive threshold remained undiminished 4 h post PGE2 administration. Inset figure shows that exposure to water avoidance stress had a large effect on nociceptive threshold, decreasing it by 33.6% and 26.8% 1 and 14 day post-stress, respectively.
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