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Metabotropic glutamate receptor 5 upregulation in A-fibers after spinal nerve injury: 2-methyl-6-(phenylethynyl)-pyridine (MPEP) reverses the induced thermal hyperalgesia.
J Neurosci. 2002 Apr 01; 22(7):2660-8.JN

Abstract

Metabotropic glutamate receptor 5 (mGluR5) protein increased after sciatic nerve section in ipsilateral L4 and L5 DRG neuronal profiles, with most of the increase occurring in myelinated A-fiber somata. mGluR5 also increased in lamina II of the ipsilateral spinal cord and the proximal sciatic nerve stump in this model. After L5 spinal nerve ligation, mGluR5 immunoreactivity increased dramatically not only in damaged L5 but also in the neighboring undamaged L4. Interestingly, after partial sciatic nerve section, mGluR5 expression did not change in either L4 or L5 DRG neuronal profiles. Both spinal nerve ligation and sciatic nerve partial section produced significant mechanical and thermal hyperalgesia and tactile allodynia. After partial sciatic nerve section, the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) had no effect on any of these behaviors. However, after L5 spinal nerve ligation, although MPEP failed to alter the induced tactile allodynia or mechanical hyperalgesia, it dose dependently reversed the developed thermal hyperalgesia. Therefore, reversal of thermal hyperalgesia by MPEP correlates with increased mGluR5 in lumbar DRG A-fiber somata after nerve injury. Furthermore, A-fibers in the uninjured L4 DRG after L5 spinal nerve ligation that have increased mGluR5 are the same A-fibers that newly express vanilloid receptor 1 after such injury. Together, these results suggest that, after L5 spinal nerve injury, mGluR5 expression on A-fibers is essential to the development of thermal hyperalgesia. After partial nerve section, however, it is unlikely that thermal responses are mediated through mGluR5 because no such increase in mGluR5 is detected in this model and MPEP is ineffective.

Authors+Show Affiliations

Oxford GlycoSciences Ltd., Abingdon, OX14 4RY, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11923431

Citation

Hudson, Lindsey J., et al. "Metabotropic Glutamate Receptor 5 Upregulation in A-fibers After Spinal Nerve Injury: 2-methyl-6-(phenylethynyl)-pyridine (MPEP) Reverses the Induced Thermal Hyperalgesia." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 22, no. 7, 2002, pp. 2660-8.
Hudson LJ, Bevan S, McNair K, et al. Metabotropic glutamate receptor 5 upregulation in A-fibers after spinal nerve injury: 2-methyl-6-(phenylethynyl)-pyridine (MPEP) reverses the induced thermal hyperalgesia. J Neurosci. 2002;22(7):2660-8.
Hudson, L. J., Bevan, S., McNair, K., Gentry, C., Fox, A., Kuhn, R., & Winter, J. (2002). Metabotropic glutamate receptor 5 upregulation in A-fibers after spinal nerve injury: 2-methyl-6-(phenylethynyl)-pyridine (MPEP) reverses the induced thermal hyperalgesia. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 22(7), 2660-8.
Hudson LJ, et al. Metabotropic Glutamate Receptor 5 Upregulation in A-fibers After Spinal Nerve Injury: 2-methyl-6-(phenylethynyl)-pyridine (MPEP) Reverses the Induced Thermal Hyperalgesia. J Neurosci. 2002 Apr 1;22(7):2660-8. PubMed PMID: 11923431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabotropic glutamate receptor 5 upregulation in A-fibers after spinal nerve injury: 2-methyl-6-(phenylethynyl)-pyridine (MPEP) reverses the induced thermal hyperalgesia. AU - Hudson,Lindsey J, AU - Bevan,Stuart, AU - McNair,Kara, AU - Gentry,Clive, AU - Fox,Alyson, AU - Kuhn,Rainer, AU - Winter,Janet, PY - 2002/3/30/pubmed PY - 2002/4/12/medline PY - 2002/3/30/entrez SP - 2660 EP - 8 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 22 IS - 7 N2 - Metabotropic glutamate receptor 5 (mGluR5) protein increased after sciatic nerve section in ipsilateral L4 and L5 DRG neuronal profiles, with most of the increase occurring in myelinated A-fiber somata. mGluR5 also increased in lamina II of the ipsilateral spinal cord and the proximal sciatic nerve stump in this model. After L5 spinal nerve ligation, mGluR5 immunoreactivity increased dramatically not only in damaged L5 but also in the neighboring undamaged L4. Interestingly, after partial sciatic nerve section, mGluR5 expression did not change in either L4 or L5 DRG neuronal profiles. Both spinal nerve ligation and sciatic nerve partial section produced significant mechanical and thermal hyperalgesia and tactile allodynia. After partial sciatic nerve section, the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) had no effect on any of these behaviors. However, after L5 spinal nerve ligation, although MPEP failed to alter the induced tactile allodynia or mechanical hyperalgesia, it dose dependently reversed the developed thermal hyperalgesia. Therefore, reversal of thermal hyperalgesia by MPEP correlates with increased mGluR5 in lumbar DRG A-fiber somata after nerve injury. Furthermore, A-fibers in the uninjured L4 DRG after L5 spinal nerve ligation that have increased mGluR5 are the same A-fibers that newly express vanilloid receptor 1 after such injury. Together, these results suggest that, after L5 spinal nerve injury, mGluR5 expression on A-fibers is essential to the development of thermal hyperalgesia. After partial nerve section, however, it is unlikely that thermal responses are mediated through mGluR5 because no such increase in mGluR5 is detected in this model and MPEP is ineffective. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/11923431/Metabotropic_glutamate_receptor_5_upregulation_in_A_fibers_after_spinal_nerve_injury:_2_methyl_6__phenylethynyl__pyridine__MPEP__reverses_the_induced_thermal_hyperalgesia_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=11923431 DB - PRIME DP - Unbound Medicine ER -