Journal article
Increased bilateral expression of α1-adrenoceptors on peripheral nerves, blood vessels and keratinocytes does not account for pain or neuroinflammatory changes after distal tibia fracture in rats
Neuroscience, Vol.281, pp.99-109
2014
Abstract
In certain forms of nerve injury and inflammation, noradrenaline augments pain via actions on up-regulated α1-adrenoceptors (α1-ARs). The aim of this study was to use immunohistochemistry to examine α1-AR expression on peripheral neurons, cutaneous blood vessels and keratinocytes after distal tibia fracture and cast immobilization, a model of complex regional pain syndrome type 1. We hypothesized that there would be increased α1-AR expression on neurons and keratinocytes in the injured limb in comparison to the contralateral unaffected limb after distal tibia fracture, in association with inflammatory changes and pain. α1-AR expression was increased on plantar keratinocytes, dermal blood vessels and peripheral nerve fibers at 16 weeks after injury both in the fractured and contralateral uninjured limb. Similar changes were seen in controls whose limb had been immobilized in a cast for 4 weeks but not fractured. Neurofilament 200 (NF200), a marker of myelinated neurons, and calcitonin gene-related peptide (CGRP), a neuropeptide involved in neuro-inflammatory signaling, decreased 4 weeks after fracture and casting but then increased at the 16-week time point. As some of these changes were also detected in the contralateral hind limb, they probably were triggered by a systemic response to fracture and casting. Soon after the cast was removed, intraplantar injections of the α1-AR antagonist prazosin released local vasoconstrictor tone but had no effect on pain behaviors. However, systemic injection of prazosin inhibited behavioral signs of pain, suggesting that fracture and/or casting triggered an up-regulation of α1-ARs in central nociceptive pathways that augmented pain. Together, these findings indicate that α1-AR expression increases in the hind limbs after distal tibia fracture and cast immobilization. However, these peripheral increases do not contribute directly to residual pain.
Details
- Title
- Increased bilateral expression of α1-adrenoceptors on peripheral nerves, blood vessels and keratinocytes does not account for pain or neuroinflammatory changes after distal tibia fracture in rats
- Authors/Creators
- E.S. Drummond (Author/Creator) - Murdoch UniversityL.F. Dawson (Author/Creator) - Murdoch UniversityP.M. Finch (Author/Creator) - Murdoch UniversityW. Li (Author/Creator) - VA Palo Alto Health Care SystemT-Z Guo (Author/Creator) - VA Palo Alto Health Care SystemW.S. Kingery (Author/Creator) - VA Palo Alto Health Care SystemP.D. Drummond (Author/Creator) - Murdoch University
- Publication Details
- Neuroscience, Vol.281, pp.99-109
- Publisher
- Elsevier
- Identifiers
- 991005540395707891
- Copyright
- Elsevier
- Murdoch Affiliation
- Centre for Research on Chronic Pain and Inflammatory Diseases; School of Psychology
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.43 Anesthesiology
- 1.43.1905 Complex Regional Pain Syndrome
- Web Of Science research areas
- Neurosciences
- ESI research areas
- Neuroscience & Behavior