Abstract
Following inflammation, primary sensory neurons in the dorsal root ganglion (DRG) alter the production of several proteins. Most DRG neurons are glutamatergic, using glutaminase as the enzyme for glutamate production, but little is known about glutaminase following inflammation. In the present study, adjuvant-induced arthritis (AIA) was produced in rats with complete Freund's adjuvant into the hindpaw. At 7 days of AIA, DRG were examined with glutaminase immunohistochemistry, Western blot immunoreactivity, and enzyme activity. Image analysis revealed that glutaminase was elevated most in small-sized neurons (21%) (P < 0.05). Western blot analysis revealed a 19% increase (P < 0.05) in total glutaminase and 21% in mitochondrial glutaminase (P < 0.05). Glutaminase enzyme activity was elevated 29% (P < 0.001) from 2.20 to 2.83 moles/kg/hr. Elevated glutaminase in primary sensory neurons could lead to increased glutamate production in spinal primary afferent terminals contributing to central sensitization or in the peripheral process contributing to peripheral sensitization.
Highlights
Several animal models of tonic pain, for example, subcutaneous and intraarticular injections of inflammatory agents such as complete Freund’s adjuvant (CFA), are used to mimic human chronic pain [1]
The fixative used in the current study provides a more accurate immunohistochemical staining pattern with all dorsal root ganglion (DRG) neurons exhibiting GLS immunoreactivity [26]
The overall GLS-IR intensity of small (
Summary
Several animal models of tonic pain, for example, subcutaneous and intraarticular injections of inflammatory agents such as complete Freund’s adjuvant (CFA), are used to mimic human chronic pain [1]. Sensory neurons respond chronically to inflammation by increasing neurotransmitter/neuromodulator, for example, tachykinin (substance P (SP)) and calcitonin gene-related peptide (CGRP), expression and content in dorsal root ganglia (DRG) [4,5,6], and enhanced immunoreactivity in the spinal dorsal horn [7], skin, and joints [8, 9]. These peptidergic neurons are glutamatergic [10, 11], using glutaminase (GLS) as the synthetic enzyme for neurotransmitter glutamate production [3, 12]. After the induction of knee joint inflammation in monkeys, glutamate-immunoreactive fibers in the spinal cord increase 30% at 4 hr and nearly 40% at
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