The Antinociceptive Potential of Camellia japonica Leaf Extract, (-)-Epicatechin, and Rutin against Chronic Constriction Injury-Induced Neuropathic Pain in Rats.

Eun Yeong Lim,Yun Tai Kim,Changho Lee

doi:10.3390/antiox11020410

Abstract

Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. Camellia japonica leaves are known to have antioxidant and anti-inflammatory properties.; however, their antinociceptive efficacy has not yet been explored. We examined the antinociceptive efficacy and underlying mechanism of C. japonica leaf extract (CJE) in chronic constriction injury (CCI)-induced neuropathic pain models. To test the antinociceptive activity of CJE, three types of allodynia were evaluated: punctate allodynia using von Frey filaments, dynamic allodynia using a paintbrush and cotton swab, and cold allodynia using a cold plate test. CCI rats developed neuropathic pain representing increases in the three types of allodynia and spontaneous pain. In addition, CCI rats showed high phosphorylation levels of mitogen-activated protein kinases (MAPKs), transcription factors, and nociceptive mediators in dorsal root ganglion (DRG). The ionized calcium-binding adapter molecule 1 levels and neuroinflammation also increased following CCI surgery in the spinal cord. CJE and its active components have potential antinociceptive effects against CCI-induced neuropathic pain that might be mediated by MAPK activation in the DRG and microglial activation in the spinal cord. These findings suggest that CJE, (−)-epicatechin, and rutin could be novel candidates for neuropathic pain management.

Highlights

Neuropathic pain is a chronic condition resulting from a lesion or disease of the somatosensory nervous system and is caused by various conditions, including strokes, multiple sclerosis, spinal cord injury, diabetic neuropathy, and postherpetic neuralgia [1,2].The prevalence of neuropathic pain is estimated at 6.9–10% globally [3]
This study evaluated the analgesic effects of C. japonica leaf extract (CJE) and its active components and elucidated their mechanisms of action in constriction injury (CCI)-induced neuropathic pain
Following CCI, the pain response to punctate allodynia was increased in CCI rats, with increased frequency elicited by 2 and 10 g von Frey filament stimulation (Figure 1B–E) and decreased Mechanical Withdrawal Threshold (MWT) in the von Frey filament test (Figure 1F,G)

Summary

Introduction

Neuropathic pain is a chronic condition resulting from a lesion or disease of the somatosensory nervous system and is caused by various conditions, including strokes, multiple sclerosis, spinal cord injury, diabetic neuropathy, and postherpetic neuralgia [1,2]. The prevalence of neuropathic pain is estimated at 6.9–10% globally [3]. The clinical symptoms of neuropathic pain manifest as both stimulus-independent (spontaneous) and stimulus-dependent (evoked) pain [4]. Evoked pain includes hyperalgesia (abnormally increased pain sensation to a noxious stimulus) and allodynia (pain sensation to a nonnoxious stimulus), which seriously affect a patient’s quality of life, incurring extreme economic burdens [5]. Many studies have attempted to elucidate the neuropathic pain mechanism and explore novel therapies for treating neuropathic pain

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