Abstract
Glutamate is a neurotransmitter used at both the peripheral and central terminals of nociceptive primary sensory neurons, yet little is known concerning regulation of glutamate metabolism during peripheral inflammation. Glutaminase (GLS) is an enzyme of the glutamate-glutamine cycle that converts glutamine into glutamate for neurotransmission and is implicated in producing elevated levels of glutamate in central and peripheral terminals. A potential mechanism for increased levels of glutamate is an elevation in GLS expression. We assessed GLS expression after unilateral hind paw inflammation by measuring GLS immunoreactivity (ir) with quantitative image analysis of L4 dorsal root ganglion (DRG) neurons after one, two, four, and eight days of adjuvant-induced arthritis (AIA) compared to saline injected controls. No significant elevation in GLS-ir occurred in the DRG ipsilateral to the inflamed hind paw after one or two days of AIA. After four days AIA, GLS-ir was elevated significantly in all sizes of DRG neurons. After eight days AIA, GLS-ir remained elevated in small (<400 µm2), presumably nociceptive neurons. Western blot analysis of the L4 DRG at day four AIA confirmed the elevated GLS-ir. The present study indicates that GLS expression is increased in the chronic stage of inflammation and may be a target for chronic pain therapy.
Highlights
IntroductionTerminate in spinal cord dorsal horn and medullary dorsal column nuclei for pain and touch pathways, respectively [1]
Central axons of pseudounipolar primary sensory neurons of the dorsal root ganglion (DRG)terminate in spinal cord dorsal horn and medullary dorsal column nuclei for pain and touch pathways, respectively [1]
Baseline mechanical thresholds of the to the complete Freund’s adjuvant (CFA) injection were not significantly different than the other baseline measurements, but they hind paws ipsilateral to the CFA injection were not significantly different than the other baseline were always significantly different from the three other groups after the injection at day 0 through measurements, but they were always significantly different from the three other groups after the day 8injection (Figureat1B)
Summary
Terminate in spinal cord dorsal horn and medullary dorsal column nuclei for pain and touch pathways, respectively [1]. Peripheral axons of these neurons terminate in and bring sensory information from target tissues, such as viscera, muscle and skin. The central axon terminals release the neurotransmitter glutamate at both spinal [2,3,4,5] and medullary levels [2]. Inflammation of peripheral target tissues increases the amount of glutamate released from both the peripheral [9,10] and central axon terminals of DRG neurons [3,4].
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