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Physical disuse could lead to a state of chronic pain typified by complex regional pain syndrome type I due to fear of pain through movement (kinesiophobia) or inappropriate resting procedures. However, the mechanisms by which physical disuse is associated with acute/chronic pain and other pathological signs remain unresolved. We have previously reported that inflammatory signs, contractures, disuse muscle atrophy, spontaneous pain-like behaviors, and chronic widespread mechanical hyperalgesia based on central plasticity occurred after 2-weeks of cast immobilization in chronic post-cast pain (CPCP) rat model. In the present study, we also demonstrated dystrophy-like changes, both peripheral nociceptive signals and activation of the central pain pathway in CPCP rats. This was done by the following methods: (1) vascular permeability (Evans blue dye) and inflammatory- and oxidative stress-related messenger RNA (mRNA) changes (real-time quantitative polymerase chain reaction); (2) immunofluorescence of pERK and/or c-Fos expression in the spino-parabrachio-amygdaloid pathway; and (3) blockade of nociceptive-related signals using sciatic nerve block (SNB). Furthermore, we demonstrated tactile allodynia using an optogenetic method in a transgenic rat line (W-TChR2V4), cold allodynia using the acetone test, and activation of dorsal horn neurons in the chronic phase associated with chronic mechanical hyperalgesia using c-Fos immunofluorescence. In addition, we showed that nociceptive signals in the acute phase are involved in chronic pathological pain-like behaviors by studying the effects of SNB. Thus, we conclude that physical disuse contributes to dystrophy-like changes, spontaneous pain-like behavior, and chronic widespread pathological pain-like behaviors in CPCP rats after 2 weeks of cast immobilization.

Background and Purpose —Inducible cyclooxygenase (COX-2) has been found to play a pathological role in cerebral insult . We investigated the expression of COX-2 in the basilar artery after experimental subarachnoid hemorrhage (SAH). Methods —In a canine “two-hemorrhage” model of SAH, the basilar arteries were obtained on day 2 after a cisternal injection of autologous blood or on days 4, 6, 7, or 9 after the second injection. Basilar arteries also were obtained 12 hours after intracisternal injection a cytokine: interleukin (IL)-1β (0.03 μg), IL-6 (3 μg), or IL-8 (10 μg). Western blotting with a polyclonal anti–COX-2 antibody was performed in these arteries. Results —COX-2 protein was not demonstrated in the basilar artery in control animals without SAH. However, it was expressed in the basilar artery on days 2, 4, 6, and 7 after blood injection but not on day 9 . Intracisternal injection of IL-1β, IL-6, or IL-8 also induced COX-2 in the basilar artery. Conclusions —COX-2 expression was detected in basilar arterial tissue in both acute and chronic stages after SAH. Elevation of inflammatory cytokines after SAH may be involved in the induction of COX-2, which may produce sufficient quantities of eicosanoids to affect hemodynamics after SAH.