Transient receptor potential ankyrin 1 in spinal cord dorsal horn is involved in neuropathic pain in nerve root constriction rats.

Abstract

BACKGROUND:

Lumbar radicular pain is categorized as a type of neuropathic pain, but its pathophysiological mechanisms are not fully understood. The substantia gelatinosa (SG) in the spinal cord dorsal horn receives primary afferent inputs and is considered to be a therapeutic target for treating neuropathic pain. In vivo patch-clamp recording is a useful procedure for analyzing the functional properties of synaptic transmission in SG neurons. Transient receptor potential ankyrin 1 (TRPA1) has been widely identified in the central and peripheral nervous systems, such as in the peripheral nociceptor, dorsal root ganglion, and spinal cord dorsal horn and is involved in synaptic transmission of pain. However, its functional role and mechanism of pain transmission in the spinal cord dorsal horn are not well understood. The purpose of this study was to use in vivo patch-clamp analysis to examine changes in the excitatory synaptic transmission of SG neurons treated with TRPA1 antagonist and to clarify the potential role of TRPA1 in the rat spinal cord dorsal horn.

RESULTS:

The rats with root constriction (RC) showed mechanical hypersensitivity, hyperalgesia, and thermal hyperalgesia. In addition, pin pricks elicited pain-related behavior even in the sham and naïve rats. These pain-related behaviors were significantly attenuated by intrathecal injection of a TRPA1 antagonist. The degrees of intrathecal injection efficacy were equivalent among the 3 groups (RC, sham, and naïve groups). In an electrophysiological study, the frequencies and amplitudes of excitatory postsynaptic currents (EPSCs) were significantly increased in the RC rats compared with those in the sham and naïve rats. Spontaneous EPSCs and evoked-EPSCs by non-noxious and noxious stimuli were significantly decreased by TRPA1 antagonist. As in the behavioral study, there were no statistically significant differences among the 3 groups.

CONCLUSION:

These data showed that the TRPA1 antagonist had an inhibitory effect on mechanical hypersensitivity and hyperalgesia as well as on physiological pain transmission in the spinal cord dorsal horn. This suggests that TRPA1 is consistently involved in excitatory synaptic transmission even in the physiological state and has a role in coordinating pain transmission.

• Authors: Tsuyoshi Miyakawa, Yoshinori Terashima, Tsuneo Takebayashi, Katsumasa Tanimoto, Takehito Iwase, Izaya Ogon, Takeshi Kobayashi, Noritsugu Tohse, Toshihiko Yamashita
• Journal: Molecular pain (Mol Pain) Vol. 10 Pg. 58 (Sep 06 2014) ISSN: 1744-8069 [Electronic] United States
• PMID: 25192906 (Publication Type: Journal Article)

Chemical References

• 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
• Acetanilides
• Purines
• TRPA1 Cation Channel
• TRPC Cation Channels
• Trpa1 protein, rat

Topics

• Acetanilides (pharmacology, therapeutic use)
• Animals
• Constriction
• Disease Models, Animal
• Excitatory Postsynaptic Potentials (drug effects)
• Hyperalgesia (etiology)
• Male
• Membrane Potentials (drug effects, physiology)
• Pain Measurement (drug effects)
• Pain Threshold (drug effects)
• Patch-Clamp Techniques
• Purines (pharmacology, therapeutic use)
• Radiculopathy (complications, drug therapy, etiology, pathology)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord Dorsal Horn (metabolism)
• Statistics, Nonparametric
• TRPA1 Cation Channel
• TRPC Cation Channels (antagonists & inhibitors, metabolism)
• Time Factors