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Molecular Pain
Published in: Molecular Pain 1/2014

Open Access 01-12-2014 | Research

Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia

Authors: Wei-Nan Chen, Cheng-Han Lee, Shing-Hong Lin, Chia-Wen Wong, Wei-Hsin Sun, John N Wood, Chih-Cheng Chen

Published in: Molecular Pain | Issue 1/2014

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Abstract

Background

Tissue acidosis is effective in causing chronic muscle pain. However, how muscle nociceptors contribute to the transition from acute to chronic pain is largely unknown.

Results

Here we showed that a single intramuscular acid injection induced a priming effect on muscle nociceptors of mice. The primed muscle nociceptors were plastic and permitted the development of long-lasting chronic hyperalgesia induced by a second acid insult. The plastic changes of muscle nociceptors were modality-specific and required the activation of acid-sensing ion channel 3 (ASIC3) or transient receptor potential cation channel V1 (TRPV1). Activation of ASIC3 was associated with increased activity of tetrodotoxin (TTX)-sensitive voltage-gated sodium channels but not protein kinase Cϵ (PKCϵ) in isolectin B4 (IB4)-negative muscle nociceptors. In contrast, increased activity of TTX-resistant voltage-gated sodium channels with ASIC3 or TRPV1 activation in NaV1.8-positive muscle nociceptors was required for the development of chronic hyperalgesia. Accordingly, compared to wild type mice, NaV1.8-null mice showed briefer acid-induced hyperalgesia (5 days vs. >27 days).

Conclusion

ASIC3 activation may manifest a new type of nociceptor priming in IB4-negative muscle nociceptors. The activation of ASIC3 and TRPV1 as well as enhanced NaV1.8 activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain.
Appendix
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Literature
1.
2.
Arendt-Nielsen L, Fernandez-de-las-Penas C, Graven-Nielsen T: Basic aspects of musculoskeletal pain: from acute to chronic pain. J Man Manip Ther 2011, 19: 186–193.PubMedCentralPubMedCrossRef
3.
DeSantana JM, Sluka KA: Central mechanisms in the maintenance of chronic widespread noninflammatory muscle pain. Curr Pain Headache Rep 2008, 12: 338–343.PubMedCentralPubMedCrossRef
4.
Staud R: Peripheral pain mechanisms in chronic widespread pain. Best Pract Res Clin Rheumat 2011, 25: 155–164.CrossRef
5.
6.
Bogen O, Alessandri-Harber N, Chu C, Gear RW, Levine JD: Generation of a pain memory in the primary afferent nociceptor triggered by PKCϵ activation of CPEB. J Neurosci 2012, 32: 2018–2026.PubMedCentralPubMedCrossRef
7.
Dina OA, McCarter GC, de Coupade C, Levine JD: Role of the sensory neuron cytoskeleton in second messenger signaling for inflammatory pain. Neuron 2003, 39: 613–624.PubMedCrossRef
8.
9.
Frey Law LA, Sluka KA, McMullen T, Lee J, Arendt-Nielsen L, Graven-Nielsen T: Acidic buffer induced muscle pain evokes referred pain and mechanical hyperalgesia in humans. Pain 2008, 140: 254–264.PubMedCrossRef
10.
Issberner U, Reeh PW, Steen KH: Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia? Neurosci Lett 1996, 208: 191–194.PubMedCrossRef
11.
Birdsong WT, Fierro L, Williams FG, Spelta V, Naves LA, Knowles M, March-Haffner J, Adelman JP, Almers W, Elde RP, McCleskey EW: Sensing muscle ischemia: coincident detection of acid and ATP via interplay of two ion channels. Neuron 2010, 68: 739–749.PubMedCentralPubMedCrossRef
12.
Fujii Y, Ozaki N, Taguchi T, Mizumura K, Furukawa K, Sugiura Y: TRP channels and ASICs mediate mechanical hyperalgesia in models of inflammatory muscle pain and delayed onset muscle soreness. Pain 2008, 140: 292–304.PubMedCrossRef
13.
Hoheisel U, Reinohl J, Unger T, Mense S: Acidic pH and capsaicin activate mechanosensitive group IV muscle receptors in the rat. Pain 2004, 110: 149–157.PubMedCrossRef
14.
Sluka KA, Kalra A, Moore SA: Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia. Muscle Nerve 2001, 24: 37–46.PubMedCrossRef
15.
Sluka KA, Price MP, Breese NM, Stucky CL, Wemmie , Welsh MJ: Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain 2003, 106: 229–239.PubMedCrossRef
16.
Oliveira LR, de Melo VU, Macedo FN, Barreto AS, Badaue-Passos D Jr, dos Santos MRV, Dias DPM, Sluka KA, DeSantana JM, Santana-Filho VJ: Induction of chronic non-inflammatory widespread pain increases cardiac sympathetic modulation in rats. Auton Neurosci 2012, 167: 45–49.PubMedCrossRef
17.
18.
Lin YW, Min MY, Lin CC, Chen WN, Wu WL, Yu HM, Chen CC: Identification and characterization of a subset of mouse sensory neurons that express acid-sensing ion channel 3. Neuroscience 2008, 151: 544–557.PubMedCrossRef
19.
Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann RE, Basbaum AI, Julius D: The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998, 21: 531–543.PubMedCrossRef
20.
Diochot S, Baron A, Rash LD, Deval E, Escoubas P, Scarzello S, Salinas M, Lazdunski M: A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J 2004, 23: 1516–1525.PubMedCentralPubMedCrossRef
21.
Lin CCJ, Chen WN, Chen CJ, Lin YW, Zimmer A, Chen CC: An antinociceptive role for substance P in acid-induced chronic muscle pain. Proc Natl Acad Sci USA 2012, 109: E76-E83.PubMedCentralPubMedCrossRef
22.
Alvarez P, Ferrari LF, Levine JD: Muscle pain in models of chemotherapy-induced and alcohol-induced peripheral neuropathy. Ann Neurol 2011, 70: 101–109.PubMedCentralPubMedCrossRef
23.
Dina OA, Joseph EK, Levine JD, Green PG: Mechanisms mediating vibration-induced chronic musculoskeletal pain analyzed in the rat. J Pain 2010, 11: 369–377.PubMedCentralPubMedCrossRef
24.
25.
Jankowski MP, Rau KK, Ekmann KM, Anderson CE, Koerber HR: Comprehensive phenotyping of group III and iV muscle afferents in mouse. J Neurophysiol 2013, 109: 2374–2381.PubMedCentralPubMedCrossRef
26.
Gautam M, Benson CJ, Ranier JD, Light AR, Sluka KA: ASICs do not play a role in maintaining hyperalgesia induced by repeated intramuscular acid injections. Pain Res Treat 2012, 2012: 817347.PubMedCentralPubMed
27.
Deval E, Noel J, Lay N, Alloui A, Diochot S, Friend V, Jodar M, Lazdunski M, Lingueglia E: ASIC3, a sensor of acidic and primary inflammatory pain. EMBO J 2008, 27: 3047–3055.PubMedCentralPubMedCrossRef
28.
Deval E, Noel J, Gasull X, Delaunay A, Alloui A, Friend V, Eschalier A, Lazdunski M, Lingueglia E: Acid-sensing ion channels in postoperative pain. J Neurosci 2011, 31: 6059–66.PubMedCrossRef
29.
Karczewski J, Spencer RH, Garsky VM, Liang A, Leitl MD, Cato MJ, Cook SP, Kane S, Urban MO: Reversal of acid-induced and inflammatory pain by the selective ASIC3 inhibitor, APETx2. Br J Pharmacol 2010, 161: 950–60.PubMedCentralPubMedCrossRef
30.
Wu WL, Cheng CF, Sun WH, Wong CW, Chen CC: Targeting ASIC3 for pain, anxiety, and insulin resistance. Pharmacol Ther 2012, 134: 127–138.PubMedCrossRef
31.
Ota H, Katanosaka K, Murase S, Kashio M, Tominaga M, Mizumura K: TRPV1 and TRPV4 play pivotal roles in delayed onset muscle soreness. PLoS ONE 2013, 8: e65751.PubMedCentralPubMedCrossRef
32.
Walder RY, Radhakrishnan R, Loo L, Rasmussen LA, Mohapatra DP, Wilson SP, Sluka KA: TRPV1 is important for mechanical and heat sensitivity in uninjured animals and development of heat hypersensitivity after muscle inflammation. Pain 2012, 153: 1664–1672.PubMedCentralPubMedCrossRef
33.
Levine JD: Alessandri-Harber: TRP channels: targets for the relief of pain. Biochim Biophys Acta 2007, 1772: 989–1003.PubMedCrossRef
34.
Zhang H, Cang CL, Kawasaki Y, Liang LL, Zhang YQ, Ji RR, Zhao ZQ: Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCϵ: a novel pathway for heat hyperalgesia. J Neurosci 2007, 27: 12067–12077.PubMedCrossRef
35.
Nielsen AN, Mathiesen C, Blackburn-Munro G: Pharmacological characterization of acid-induced muscle allodynia in rats. Eur J Pharmacol 2004, 487: 93–103.PubMedCrossRef
36.
Jarvis MF, Honore P, Shieh CC, Chapman M, Joshi S, Zhang XF, Kort M, Carroll W, Marron B, Atkinson R, Thomas J, Liu D, Krambis M, Liu Y, McGaraughty S, Chu K, Roeloffs R, Zhong C, Mikusa JP, Hernandez G, Gauvin D, Wade C, Zhu C, Pai M, Scanio M, Shi L, Drizin I, Gregg R, Matulenko M, Hakeem A, Gross M, Johnson M, Marsh K, Wagoner PK, Sullivan JP, Faltynek CR, Krafte DS: A-803467, a potent and selective Na V 1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci USA 2007, 104: 8520–5.PubMedCentralPubMedCrossRef
37.
Akopian AN, Sivilotti L, Wood JN: A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature 1996, 379: 257–62.PubMedCrossRef
38.
Eijkelkamp N, Linley JE, Baker MD, Minett MS, Cregg R, Werdehausen R, Rugiero F, Wood JN: Neurological perspectives on voltage-gated sodium channels. Brain 2012, 135: 2585–2612.PubMedCentralPubMedCrossRef
39.
Blanchard MG, Rash LD, Kellenberger S: Inhibition of voltage-gated Na + currents in sensory neurones by the sea anemone toxin APETx2. Br J Pharmacol 2012, 165: 2167–2177.PubMedCentralPubMedCrossRef
40.
Huang CW, Tzeng JN, Chen YJ, Tsai WF, Chen CC, Sun WH: Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors. Mol Cell Neurosci 2007, 36: 195–210.PubMedCrossRef
41.
Huang YH, Chang CY, Chen CC, Yang CD, Sun WH: Distinct expression of Mas1-related G-protein-coupled receptor B4 in dorsal root and trigeminal ganglia-implications for altered behaviors in acid-sensing ion channel-deficient mice. J Mol Neurosci 2013, 51: 820–834.PubMedCrossRef
42.
Su YS, Sun WH, Chen CC: Molecular mechanism of inflammatory pain. World J Anesthesiol 2014, 3: 71–81.CrossRef
43.
44.
Deval E, Gasull X, Noel J, Salinas M, Baron A, Diochot S, Lingueglia E: Acid-sensing ion channels (ASICs): pharmacology and implication in pain. Pharmacol Ther 2010, 128: 549–558.PubMedCrossRef
45.
Gautam M, Benson CJ: Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits. FASEB J 2013, 27: 793–802.PubMedCentralPubMedCrossRef
46.
47.
Alvarez P, Chen X, Bogen O, Green PG, Levine JD: IB4(+) nociceptors mediate persistent muscle pain induced by GDNF. J Neurophysiol 2012, 108: 2545–2553.PubMedCentralPubMedCrossRef
48.
49.
Hoeger-Bement MK, Sluka KA: Phosphorylation of CREB and mechanical hyperalgesia is reversed by blockade of the cAMP pathways in a time-dependent manner after repeated intramuscular acid injections. J Neurosci 2003, 23: 5437–5445.PubMed
50.
Chen WK, Liu IY, Chang YT, Chen YC, Chen CC, Yen CT, Shin HS, Chen CC: Cav3.2 T-type Ca2+ channel-dependent activtation of ERK in paraventricular thalamus modulates acid-induced chronic muscle pain. J Neurosci 2010, 30: 10360–10368.PubMedCrossRef
51.
Cheng SJ, Chen CC, Yang HW, Chang YT, Bai SW, Chen CC, Yen CT, Min MY: Role of extracellular signal-regulated kinase in synaptic transmission and plasticity of a nociceptor input on capsular central amygdaloid neurons in normal and acid-induced muscle pain mice. J Neurosci 2011, 31: 2258–2270.PubMedCrossRef
52.
Brederson JD, Jarvis MF, Honore P, Surowy CS: Fibromyalgia: mechanism, current treatment and animal models. Curr Pharmaceut Biotech 2011, 12: 1613–1626.CrossRef
53.
Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, Zimmer A: A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc Natl Acad Sci USA 2002, 99: 8992–8997.PubMedCentralPubMedCrossRef
54.
Stirling LC, Forlani G, Baker MD, Wood JN, Mattews EA, Dickenson AH, Nassar MA: Nociceptor-specific gene deletion using heterozygous Na V 1.8-Cre recombinase mice. Pain 2005, 113: 27–36.PubMedCrossRef
55.
Nakamura T, Colbert MC, Robbins J: Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system. Circ Res 2006, 98: 1547–1554.PubMedCrossRef
56.
Drew LJ, Rohrer DK, Price MP, Blaver KE, Cockayne DA, Cesare P, Wood JN: Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalia sensory neurons. J Physiol 2004, 556: 691–710.PubMedCentralPubMedCrossRef
Metadata
Title
Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia
Authors
Wei-Nan Chen
Cheng-Han Lee
Shing-Hong Lin
Chia-Wen Wong
Wei-Hsin Sun
John N Wood
Chih-Cheng Chen
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2014
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-10-40

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