Mechanisms underlying immobilization-induced muscle pain in rats
Satoshi Oga MS
Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Department of Rehabilitation, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
Search for more papers by this authorKyo Goto PhD
Department of Rehabilitation, Nagasaki Memorial Hospital, Nagasaki, Japan
Search for more papers by this authorCorresponding Author
Junya Sakamoto PhD
Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Correspondence
Junya Sakamoto PhD, Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8520, Japan.
Email: [email protected]
Search for more papers by this authorYuichiro Honda PhD
Department of Rehabilitation, Nagasaki University Hospital, Nagasaki, Japan
Search for more papers by this authorRyo Sasaki MS
Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Department of Rehabilitation, Juzenkai Hospital, Nagasaki, Japan
Search for more papers by this authorKumiko Ishikawa MS
Department of Rehabilitation, Nagasaki University Hospital, Nagasaki, Japan
Search for more papers by this authorHideki Kataoka PhD
Department of Rehabilitation, Nagasaki Memorial Hospital, Nagasaki, Japan
Search for more papers by this authorJiro Nakano PhD
Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorTomoki Origuchi MD
Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorMinoru Okita PhD
Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorSatoshi Oga MS
Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Department of Rehabilitation, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
Search for more papers by this authorKyo Goto PhD
Department of Rehabilitation, Nagasaki Memorial Hospital, Nagasaki, Japan
Search for more papers by this authorCorresponding Author
Junya Sakamoto PhD
Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Correspondence
Junya Sakamoto PhD, Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8520, Japan.
Email: [email protected]
Search for more papers by this authorYuichiro Honda PhD
Department of Rehabilitation, Nagasaki University Hospital, Nagasaki, Japan
Search for more papers by this authorRyo Sasaki MS
Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Department of Rehabilitation, Juzenkai Hospital, Nagasaki, Japan
Search for more papers by this authorKumiko Ishikawa MS
Department of Rehabilitation, Nagasaki University Hospital, Nagasaki, Japan
Search for more papers by this authorHideki Kataoka PhD
Department of Rehabilitation, Nagasaki Memorial Hospital, Nagasaki, Japan
Search for more papers by this authorJiro Nakano PhD
Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorTomoki Origuchi MD
Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorMinoru Okita PhD
Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Search for more papers by this authorFunding information: JSPS KAKENHI, Grant/Award Number: JP18K17751
Abstract
Introduction
We investigated the mechanisms underlying immobilization-induced muscle pain in rats.
Methods
In rat skeletal muscle, pressure pain threshold (PPT) of the gastrocnemius muscle was measured, and nerve growth factor (NGF) level, peripheral nerve fiber density, macrophage number, and interleukin-1β (IL-1β) mRNA expression were examined. An NGF receptor inhibitor was injected intramuscularly to assess the relationship between PPT and NGF levels.
Results
Immobilization resulted in a decrease in PPT and increases in NGF level, C-fiber density, M1 macrophage number, and IL-1β mRNA expression. Injection of NGF receptor inhibitor reversed the decrease in PPT.
Discussion
NGF upregulation may be a major contributor to immobilization-induced muscle pain. The increases in C-fiber density, M1 macrophage number, and IL-1β mRNA expression may be related to immobilization-induced muscle pain.
5 CONFLICT OF INTEREST
The authors declare no potential conflicts of interest.
Supporting Information
Filename | Description |
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mus26840-sup-0001-TableS1.docxWord 2007 document , 22.8 KB | Supplemental Table 1 Sequences of primers used in real-time RT PCR |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Boyd AS, Benjamin HJ, Asplund C. Splints and casts: indications and methods. Am Fam Phys. 2009; 80: 491-499.
- 2Booth FW. Time course of muscular atrophy during immobilization of hindlimbs in rats. J Appl Physiol Respir Environ Exerc Physiol. 1977; 43: 656-661.
- 3Okita M, Yoshimura T, Nakano J, Motomura M, Eguchi K. Effects of reduced joint mobility on sarcomere length, collagen fibril arrangement in the endomysium, and hyaluronan in rat soleus muscle. J Muscle Res Cell Motil. 2004; 25: 159-166.
- 4Guo TZ, Offley SC, Boyd EA, Jacobs CR, Kingery WS. Substance P signaling contributes to the vascular and nociceptive abnormalities observed in a tibial fracture rat model of complex regional pain syndrome type I. Pain. 2004; 108: 95-107.
- 5Terkelsen AJ, Bach FW, Jensen TS. Experimental forearm immobilization in humans induces cold and mechanical hyperalgesia. Anesthesiology. 2008; 109: 297-307.
- 6Nakano J, Sekino Y, Hamaue Y, et al. Changes in hind paw epidermal thickness, peripheral nerve distribution and mechanical sensitivity after immobilization in rats. Physiol Res. 2012; 61: 643-647.
- 7Hamaue Y, Nakano J, Sekino Y, et al. Immobilization-induced hypersensitivity associated with spinal cord sensitization during cast immobilization and after cast removal in rats. J Physiol Sci. 2013; 63: 401-408.
- 8Sekino Y, Nakano J, Hamaue Y, et al. Sensory hyperinnervation and increase in NGF, TRPV1 and P2X3 expression in the epidermis following cast immobilization in rats. Eur J Pain. 2014; 18: 639-648.
- 9Morimoto A, Winaga H, Sakurai H, et al. Treadmill running and static stretching improve long-lasting hyperalgesia, joint limitation, and muscle atrophy induced by cast immobilization in rats. Neurosci Lett. 2013; 534: 295-300.
- 10Hayashi K, Ozaki N, Kawakita K, et al. Involvement of NGF in the rat model of persistent muscle pain associated with taut band. J Pain. 2011; 12: 1059-1068.
- 11Svensson P, Cairns BE, Wang K, Arendt-Nielsen L. Injection of nerve growth factor into human masseter muscle evokes long-lasting mechanical allodynia and hyperalgesia. Pain. 2003; 104: 241-247.
- 12Murase S, Terazawa E, Queme F, et al. Bradykinin and nerve growth factor play pivotal roles in muscular mechanical hyperalgesia after exercise (delayed-onset muscle soreness). J Neurosci. 2010; 30: 3752-3761.
- 13Hayashi K, Shiozwa S, Ozaki N, Mizumura K, Graven-Nielsen T. Repeated intramuscular injections of nerve growth factor induced progressive muscle hyperalgesia, facilitated temporal summation, and expanded pain areas. Pain. 2013; 154: 2344-2352.
- 14Wong H, Kang I, Dong XD, et al. NGF-induced mechanical sensitization of the masseter muscle is mediated through peripheral NMDA receptors. Neuroscience. 2014; 269: 232-244.
- 15Chakrabarty A, McCarson KE, Smith PG. Hypersensitivity and hyperinnervation of the rat hind paw following carrageenan-induced inflammation. Neurosci Lett. 2011; 495: 67-71.
- 16Chakrabarty A, Liao Z, Smith PG. Angiotensin II receptor type 2 activation is required for cutaneous sensory hyperinnervation and hypersensitivity in a rat hind paw model of inflammatory pain. J Pain. 2013; 14: 1053-1065.
- 17Tague SE, Clarke GL, Winter MK, McCarson KE, Wright DE, Smith PG. Vitamin D deficiency promotes skeletal muscle hypersensitivity and sensory hyperinnervation. J Neurosci. 2011; 31: 13728-13738.
- 18Gong WY, Abdelhamid RE, Carvalho CS, Sluka KA. Resident macrophages in muscle contribute to development of hyperalgesia in a mouse model of noninflammatory muscle pain. J Pain. 2016; 17: 1081-1094.
- 19Zhu S, Nagashima M, Khan MA, Yasuhara S, Kaneki M, Martyn JA. Lack of caspase-3 attenuates immobilization-induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation. Muscle Nerve. 2013; 47: 711-721.
- 20Honda Y, Sakamoto J, Nakano J, et al. Upregulation of interleukin-1β/transforming growth factor-β1 and hypoxia relate to molecular mechanisms underlying immobilization-induced muscle contracture. Muscle Nerve. 2015; 52: 419-427.
- 21Ogle ME, Segar CE, Sridhar S, Botchwey EA. Monocytes and macrophages in tissue repair; implications for immunoregenerative biomaterial design. Exp Biol Med. 2016; 241: 1084-1097.
- 22da Silva MD, Bobinski F, Sato KL, Kolker SJ, Sluka KA, Santos AR. IL-10 cytokine released from M2 macrophages is crucial for analgesic and anti-inflammatory effects of acupuncture in a model of inflammatory muscle pain. Mol Neurobiol. 2015; 51: 19-31.
- 23Bobinski F, Teixeira JM, Sluka KA, Santos ARS. Interleukin-4 mediates the analgesia produced by low-intensity exercise in mice with neuropathic pain. Pain. 2018; 159: 437-450.
- 24Caron AZ, Haroun S, Leblanc E, et al. The proteasome inhibitor MG132 reduces immobilization-induced skeletal muscle atrophy in mice. BMC Musculoskelet Disord. 2011; 12: 185.
- 25Pelegrini-da-Silva A, Oliveira MC, Parada CA, Tambeli CH. Nerve growth factor acts with the beta2-adrenoceptor to induce spontaneous nociceptive behavior during temporomandibular joint inflammatory hyperalgesia. Life Sci. 2008; 83: 780-785.
- 26Lawson SN, Harper AA, Harper EI, Garson JA, Anderton BH. A monoclonal antibody against neurofilament protein specifically labels a subpopulation of rat sensory neurones. J Comp Neurol. 1984; 228: 263-272.
- 27Komori N, Neal J, Cain SD, Logan J, Wirsig C, Miller KE. Presence of beta-arrestin-1 immunoreactivity in the cutaneous nerve fibers of rat glabrous skin. Brain Res. 2003; 988: 121-129.
- 28Nasu T, Taguchi T, Mizumura K. Persistent deep mechanical hyperalgesia induced by repeated cold stress in rats. Eur J Pain. 2010; 14: 236-244.
- 29Wu C, Erickson MA, Xu J, Wild KD, Brennan TJ. Expression profile of nerve growth factor after muscle incision in the rat. Anesthesiology. 2009; 110: 140-149.
- 30Ota H, Arai T, Iwatsuki K, et al. Pathological mechanism of musculoskeletal manifestations associated with CRPS type II; an animal study. Pain. 2014; 155: 1976-1985.
- 31Hoheisel U, Unger T, Mense S. Excitatory and modulatory effects of inflammatory cytokines and neurotrophins on mechanosensitive group IV muscle afferents in the rat. Pain. 2005; 114: 168-176.
- 32Hoheisel U, Unger T, Mense S. Sensitization of rat dorsal horn neurons by NGF-induced subthreshold potentials and low-frequency activation. A study employing intracellular recordings in vivo. Brain Res. 2007; 1169: 34-43.
- 33Hefti FF, Rosenthal A, Walicke PA, et al. Novel class of pain drugs based on antagonism of NGF. Trends Pharmacol Sci. 2006; 27: 85-91.
- 34Mantyh PW, Koltzenburg M, Mendell LM, Tive L, Shelton DL. Antagonism of nerve growth factor-TrkA signaling and the relief of pain. Anesthesiology. 2011; 115: 189-204.
- 35Lewin GR, Barde YA. Physiology of the neurotrophins. Annu Rev Neurosci. 1996; 19: 289-317.
- 36Pezet S, McMahon SB. Neurotrophins; mediators and modulators on pain. Annu Rev Neurosci. 2006; 29: 507-538.
- 37Albers KM, Wright DE, Davis BM. Overexpression of nerve growth factor in epidermis of transgenic mice causes hypertrophy of the peripheral nervous system. J Neurosci. 1994; 14: 1422-1432.
- 38Wu ZX, Dey RD. Nerve growth factor-enhanced airway responsiveness involves substance P in ferret intrinsic airway neurons. Am J Physiol Lung Cell Mol Physiol. 2006; 291: 111-118.
- 39Schnegelsberg B, Sun TT, Cain G, et al. Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function. Am J Physiol Regul Integr Comp Physiol. 2010; 298: 534-547.
- 40Averill S, McMahon SB, Clary DO, Reichardt LF, Priestley JV. Immunocytochemical localization of trkA receptors in chemically identified subgroups adult rat sensory neurons. Eur J Neurosci. 1995; 7: 1484-1494.
- 41Priestley JV, Michael GJ, Averill S, Liu M, Willmott N. Regulation of nociceptive neurons by nerve growth factor and glial cell line derived neurotrophic factor. Can J Physiol Pharmacol. 2002; 80: 495-505.
- 42McMahon SB, Armanini MP, Ling LH, Phillips HS. Expression and coexpression of Trk receptors in subpopulations of adult primary sensory neurons projecting to identified peripheral targets. Neuron. 1994; 12: 1161-1171.
- 43Pierce LM, Rankin MR, Foster RT, et al. Distribution and immunohistochemical characterization of primary afferent neurons innervationg the levator ani muscle of the female squirrel monkey. Am J Obstet Gynecol. 2006; 195: 987-996.
- 44Queme F, Taguchi T, Mizumura K, Graven-Nielsen T. Muscular heat and mechanical pain sensitivity after lengthening contractions in humans and animals. J Pain. 2013; 14: 1425-1436.
- 45Nakawaki M, Uchida K, Miyagi M, et al. Changes in nerve growth factor expression and macrophage phenotype following intervertebral disc injury in mice. J Orthop Res. 2019; 37: 1798-1804.
- 46Wei T, Guo TZ, Li WW, Kingery WS, Clark JD. Acute versus chronic phase mechanisms in a rat model of CRPS. J Neuroinflamm. 2016; 13: 14.
- 47Takano S, Uchida K, Inoue G, et al. Nerve growth factor regulation and production by macrophages in osteoarthritic synovium. Clin Exp Immunol. 2017; 190: 235-243.
- 48Pogatzki EM, Gebhart GF, Brennan TJ. Characterization of Adelta- and C-fibers innervating the plantar rat hindpaw one day after an incision. J Neurophysiol. 2002; 87: 721-731.