Abstract
To elucidate the relationship between chronic pain conditions with cast immobilization and autonomic function, we investigated the functional changes of the autonomic nervous system in conscious rats with chronic post-cast pain (CPCP) induced by a two-week cast immobilization of one hind limb. We telemetrically examined the time courses of systolic arterial blood pressure (SBP), heart rate (HR), and the middle-frequency (MF) component obtained from the power spectral analysis of SBP variability as a vasomotor sympathetic index. We also investigated the baroreflex sensitivity to phentolamine, an α-adrenoceptor antagonist, and the SBP and HR responses to a low ambient temperature (LT; 9.0 ± 0.2°C) exposure, a sympathetic stimulant. Rats exposed to cast immobilization exhibited mechanical allodynia lasting for at least 10 weeks after cast removal in the calf area (skin and muscle) of the bilateral hind limbs. Under resting conditions, the SBP, HR, and MF components were significantly increased during cast immobilization (all p < 0.001). Following cast removal, these parameters gradually decreased and within 1 week reached lower than baseline levels, lasting for over 10 weeks. Phentolamine administration (10 mg/kg, intraperitoneally) significantly decreased the SBP before and during cast immobilization (before, p < 0.001; during, p = 0.001) but did not lower the SBP after cast removal. The baroreflex gain after phentolamine administration, calculated as the HR increase divided by the SBP reduction, was significantly increased after cast removal (p = 0.002). The SBP increase on LT exposure was significantly greater after cast removal than that before cast immobilization, suggesting hypersensitivity to sympathetic neurotransmitters. These results revealed that, in the CPCP model, sympathetic activation was augmented during cast immobilization, which then decreased after cast removal and remained below normal levels with persisting pain behaviors. Additionally, the responsiveness of the autonomic nervous system was impaired in the CPCP model.
Highlights
Chronic pain is often accompanied by autonomic disorders, as well as spontaneous pain, hyperalgesia, and allodynia [1,2,3,4,5]
The mechanical withdrawal thresholds decreased bilaterally after cast removal (ipsilateral, F(13,104) = 39.0; contralateral, F(13,104) = 19.1; p < 0.001 for both, n = 9). These decreased thresholds reached a minimum within 1 day after cast removal, and the significantly decreased levels lasted for 10 weeks after cast removal, this effect was gradually reduced
We examined the effects of low ambient temperature (LT) exposure on the cardiovascular parameters in chronic post-cast pain (CPCP) rats Fig 6 shows the systolic arterial blood pressure (SBP) changes during LT exposure before cast immobilization and 6 weeks after cast removal (n = 9)
Summary
Chronic pain is often accompanied by autonomic disorders, as well as spontaneous pain, hyperalgesia, and allodynia [1,2,3,4,5]. Previous studies in patients with CRPS showed that the venous level of the sympathetic neurotransmitter noradrenaline was lower in the affected limb than in the unaffected limb [13,14,15,16]. Could subsequently cause an augmented responsiveness of α-adrenoceptors on blood vessels [17, 18], resulting in a cold extremity in the chronic stage of CRPS. This is demonstrative that the activity of sympathetic neurons is normal or decreased but never increased in chronic pain conditions
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