Changes in Midbrain Pain Receptor Expression, Gait and Behavioral Sensitivity in a Rat Model of Radiculopathy

Priscilla Y Hwang1, Kyle D Allen1, 2, Mohammed F Shamji1, 3, Liufang Jing1, Brian A Mata2, Mostafa A Gabr2, Janet L Huebner4, Virginia B Kraus4, William J Richardson2, Lori A Setton*, 1, 2
1 Department of Biomedical Engineering, Duke University, Durham, NC, USA
2 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA
3 Division of Neurosurgery, The Ottawa Hospital, Ottawa, ON, Canada
4 Division of Rheumatology and Immunology, Department of Medicine, Duke University Medical Center, Durham, NC, USA

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© Hwang et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Biomedical Engineering and Orthopaedic Surgery, Box 90281, Duke University, Durham, NC 27708, USA; Tel: (919) 660-5131; Fax: (919) 660-5362; E-mail:


Intervertebral disc herniation may contribute to inflammatory processes that associate with radicular pain and motor deficits. Molecular changes at the affected dorsal root ganglion (DRG), spinal cord, and even midbrain, have been documented in rat models of radiculopathy or nerve injury. The objective of this study was to evaluate gait and the expression of key pain receptors in the midbrain in a rodent model of radiculopathy. Radiculopathy was induced by harvesting tail nucleus pulposus (NP) and placing upon the right L5 DRG in rats (NP-treated, n=12). Tail NP was discarded in sham-operated animals (n=12). Mechanical allodynia, weight-bearing, and gait were evaluated in all animals over time. At 1 and 4 weeks after surgery, astrocyte and microglial activation was tested in DRG sections. Midbrain sections were similarly evaluated for immunoreactivity to serotonin (5HT2B), mu-opioid (µ-OR), and metabotropic glutamate (mGluR4 and 5) receptor antibodies. NP-treated animals placed less weight on the affected limb 1 week after surgery and experienced mechanical hypersensitivity over the duration of the study. Astroctye activation was observed at DRGs only at 4 weeks after surgery. Findings for pain receptors in the midbrain of NP-treated rats included an increased expression of 5HT2B at 1, but not 4 weeks; increased expression of µ-OR and mGluR5 at 1 and 4 weeks (periaqueductal gray region only); and no changes in expression of mGluR4 at any point in this study. These observations provide support for the hypothesis that the midbrain responds to DRG injury with a transient change in receptors regulating pain responses.

Keywords:: Dorsal root ganglion, gait, intervertebral disc, lumbar radiculopathy, metabotropic glutamate receptor, midbrain, mu-opioid receptor, serotonin receptor.