Changes in cardiovascular parameters in rats exposed to chronic widespread mechanical allodynia induced by hind limb cast immobilization

PLoS One. 2021 Jan 19;16(1):e0245544. doi: 10.1371/journal.pone.0245544. eCollection 2021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baroreflex
  • Blood Pressure
  • Cardiovascular System / physiopathology*
  • Heart Rate
  • Hindlimb*
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology*
  • Immobilization / adverse effects*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Grants and funding

The Research Budget (2002–2008) of the Department of Algesiology, Aichi Medical University. This funding was awarded to TY, HS, YO, MO, AM. Grant number: None. URL of funder website: None. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Grants-in-Aid for Scientific Research (C) (KAKENHI No. 18613020, 20602009) from the Japan Society for the Promotion of Science. This funding was awarded to TY, HS, YO, MO, AM. Grant number: KAKENHI No. 18613020, 20602009. URL of funder website: https://www.jsps.go.jp/english/index.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Daiko Foundation (2007). This funding was awarded to TY. Grant number: 5476. URL of funder website: http://www1.s3.starcat.ne.jp/daiko-f/jyosei_07.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Research Foundation for Oriental Medicine (2007). This funding was awarded to TY. Grant number: 07-07. URL of funder website: http://www.disclo-koeki.org/07a/00928/index.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.