ASICs Do Not Play a Role in Maintaining Hyperalgesia Induced by Repeated Intramuscular Acid Injections

Mamta Gautam,Christopher J Benson,Alan R Light,Kathleen A Sluka,Jon D Ranier

doi:10.1155/2012/817347

Mamta Gautam, Christopher J Benson + Show 3 more

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https://doi.org/10.1155/2012/817347

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Abstract

Repeated intramuscular acid injections produce long-lasting mechanical hyperalgesia that depends on activation of ASICs. The present study investigated if pH-activated currents in sensory neurons innervating muscle were altered in response to repeated acid injections, and if blockade of ASICs reverses existing hyperalgesia. In muscle sensory neurons, the mean acid-evoked current amplitudes and the biophysical properties of the ASIC-like currents were unchanged following acidic saline injections when compared to neutral pH saline injections or uninjected controls. Moreover, increased mechanical sensitivity of the muscle and paw after the second acid injection was unaffected by local blockade of ASICs (A-317567) in the muscle. As a control, electron microscopic analysis showed that the tibial nerve was undamaged after acid injections. Our previous studies demonstrated that ASICs are important in the development of hyperalgesia to repeated acid injections. However, the current data suggest that ASICs are not involved in maintaining hyperalgesia to repeated intramuscular acid injections.

Highlights

Acid Sensing Ion Channels (ASICs) are found in peripheral neurons and play a significant role in modulation of nociceptive behavior following insult to muscle or joint
The transient component properties are characteristic of ASICs [6, 22], whereas the sustained component can represent activation of transient receptor potential subfamily vanilloid 1 (TRPV1) channels in DRG neurons [24]
We previously demonstrated that the transient component of pH-activated currents in muscle DRG neurons was blocked by the ASIC inhibitor, amiloride, and was unaffected by the TRPV1 inhibitor, capsazepine [18]

Summary

Introduction

Acid Sensing Ion Channels (ASICs) are found in peripheral neurons and play a significant role in modulation of nociceptive behavior following insult to muscle or joint. Restoration of ASIC3 expression in primary afferent fibers innervating muscle of ASIC3−/− mice rescues mechanical hyperalgesia after muscle inflammation [7], suggesting a significant role for peripheral ASIC3 in inflammatory hyperalgesia from muscle. Inflammation induces an increased mRNA (ASIC1 and ASIC3) and protein expression (ASIC3) in DRG and increased protein expression in peripheral terminals of nociceptors [8,9,10, 15,16,17,18]. This enhanced expression in DRG is manifested as an increased responsiveness to acidic pH [19]. Inflammatory hyperalgesia is reversed by blockade of ASICs nonselectively, or by selective blockade of ASIC3

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