Hydrogen Peroxide Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors

Abstract

Background H2O2 has a variety of actions in skin wounds but has been rarely studied in deep muscle tissue. Based on response to the transient receptor potential ankyrin 1 antagonists after plantar incision, we hypothesized that H2O2 exerts nociceptive effects via the transient receptor potential ankyrin 1 in muscle. Methods Nociceptive behaviors in rats (n = 269) and mice (n = 16) were evaluated after various concentrations and volumes of H2O2 were injected into the gastrocnemius muscle or subcutaneous tissue. The effects of H2O2 on in vivo spinal dorsal horn neuronal activity and lumbar dorsal root ganglia neurons in vitro were evaluated from 26 rats and 6 mice. Results Intramuscular (mean ± SD: 1,436 ± 513 s) but not subcutaneous (40 ± 58 s) injection of H2O2 (100 mM, 0.6 ml) increased nociceptive time. Conditioned place aversion was evident after intramuscular (–143 ± 81 s) but not subcutaneous (–2 ± 111 s) injection of H2O2. These H2O2-induced behaviors were blocked by transient receptor potential ankyrin 1 antagonists. Intramuscular injection of H2O2 caused sustained in vivo activity of dorsal horn neurons, and H2O2 activated a subset of dorsal root ganglia neurons in vitro. Capsaicin nerve block decreased guarding after plantar incision and reduced nociceptive time after intramuscular H2O2. Nociceptive time after intramuscular H2O2 in transient receptor potential ankyrin 1 knockout mice was shorter (173 ± 156 s) compared with wild-type mice (931 ± 629 s). Conclusions The greater response of muscle tissue to H2O2 may help explain why incision that includes deep muscle but not skin incision alone produces spontaneous activity in nociceptive pathways.

Roles of TRPV1 and TRPA1 in Spontaneous Pain from Inflamed Masseter Muscle

“…TRPA1 is activated by multiple products from oxidative stress including H 2 O 2 (Andersson et al, 2008). Scavenging H 2 O 2 by peripheral injection of catalase, an H 2 O 2 -detoxifying enzyme, attenuates inflammatory hyperalgesia (Trevisan et al, 2014), and direct injection of H 2 O 2 produces muscle pain by activation of TRPA1 (Sugiyama et al, 2017). To test the effects of scavenging H 2 O 2 at the site of masseter inflammation, catalase was injected into masseter muscle 1 day after CFA injection.…”

“…TRPV1, a capsaicin receptor, is endogenously activated by oxidized lipids (Chung et al, 2011; Ruparel et al, 2012); TRPA1 is activated by natural compounds such as mustard oil, and by multiple endogenous electrophiles such as hydrogen peroxide (H 2 O 2 ) (Chung et al, 2011; Trevisan et al, 2014; Sugiyama et al, 2017). TRPV1 contributes to cutaneous thermal hyperalgesia, and TRPA1 contributes to cutaneous cold and mechanical hyperalgesia (Chung et al, 2011).…”

Peripheral Mechanisms of Ischemic Myalgia

“…These sensory neurons also respond to a variety of stimuli including mechanical deformation of the muscles, a wide range of temperatures and changes in the intramuscular chemical environment that includes protons, various metabolites (e.g. : lactate, ATP, ADP) or in some cases noxious free radicals like hydrogen peroxide (Mense and Schmidt, 1974 ; Kumazawa and Mizumura, 1976 ; Kaufman et al, 1984 ; Iwamoto et al, 1985 ; Delliaux et al, 2009 ; Xu and Brennan, 2009 ; McCord et al, 2010 ; Jankowski et al, 2013 ; Sugiyama et al, 2017a , b ).…”

Pharmacological validation of voluntary gait and mechanical sensitivity assays associated with inflammatory and neuropathic pain in mice

“…In recent years in the area of pain research, newer assays of pain in rodent models, such as wheel running, burrowing, gait, ultrasonic vocalization, conditioned place preference etc. have been developed (Vrinten and Hamers 2003, Li, Rhodes et al 2004, Williams, Riskin et al 2008, King, Vera-Portocarrero et al 2009, Truin, van Kleef et al 2009, Kurejova, Nattenmuller et al 2010, Mogil, Graham et al 2010, Andrews, Legg et al 2012, Cobos, Ghasemlou et al 2012, Huehnchen, Boehmerle et al 2013, Parvathy and Masocha 2013, Ruan, Patel et al 2013, Chiang, Sheu et al 2014, Muramatsu, Sasho et al 2014, Rutten, Robens et al 2014, Sahbaie, Sun et al 2014, Gould, Doods et al 2016, Pitzer, Kuner et al 2016, Wodarski, Delaney et al 2016, Sheahan, Siuda et al 2017, Sugiyama, Kang et al 2017) in an effort to improve the translational potential of preclinical findings (Barrot 2012, Tappe-Theodor and Kuner 2014, Clark 2016). However, most of these newer and operant-based assays haven’t shown universality across different pain types, such as inflammatory, neuropathic, and specific disease-related.…”