Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats.

Masamichi Shinoda,Masatoshi Ando,Yoshinori Hayashi,Masayuki Kobayashi,Koichi Iwata,Shintaro Fujiwara,Takaaki Tamagawa,Sayaka Asano,Ryo Koyama,Yuki Kimura,Satoshi Fujita,Tomoyuki Matsui,Kumi Soma,Shiori Sugawara,Daisuke Ikutame,Takamitsu Yamamoto,Kazutaka Kobayashi,Ayaka Osada,Kuniko Kusama-Eguchi

doi:10.3390/ijms21072390

Masamichi Shinoda, Masatoshi Ando + Show 17 more

Open Access

https://doi.org/10.3390/ijms21072390

Copy DOI

Abstract

We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4-S1 spinal cord. The effects of SCS and intraperitoneal minocycline administration on plantar mechanical sensitivity, microglial activation, and neuronal excitability in the L4 dorsal horn were assessed on day 3 after SNI. The somatosensory cortical responses to electrical stimulation of the hind paw on day 3 following SNI were examined by using in vivo optical imaging with a voltage-sensitive dye. On day 3 after SNI, plantar mechanical hypersensitivity and enhanced microglial activation were suppressed by minocycline or SCS, and L4 dorsal horn nociceptive neuronal hyperexcitability was suppressed by SCS. In vivo optical imaging also revealed that electrical stimulation of the hind paw-activated areas in the somatosensory cortex was decreased by SCS. The present findings suggest that SCS could suppress plantar SNI-induced neuropathic pain via inhibition of microglial activation in the L4 dorsal horn, which is involved in spinal neuronal hyperexcitability. SCS is likely to be a potential alternative and complementary medicine therapy to alleviate neuropathic pain following nerve injury.

Highlights

Neuropathic pain such as postherpetic neuralgia, post-stroke pain, and trigeminal neuralgia is known to occur as a result of peripheral and/or central neurological disturbances [1]
To evaluate the mechanisms underlying the spinal cord stimulation (SCS)-induced modulation of neuropathic pain associated with sciatic nerve injury, we examined the effect of SCS on mechanical hypersensitivity and dorsal horn microglial activation, and assessed neuronal hyperexcitability in the dorsal horn following sciatic nerve injury
SCS for six hours successively significantly recovered the decrement of Paw withdrawal thresholds (PWTs) at 30 min post-SCS (post-sham stimulation (n = 6), SCS (n = 7), p = 0.01)

Summary

Introduction

Neuropathic pain such as postherpetic neuralgia, post-stroke pain, and trigeminal neuralgia is known to occur as a result of peripheral and/or central neurological disturbances [1]. Neuropathic pain is clinically typified by intractable non-noxious stimulation-induced pain and thought to be a direct result of a lesion or disease that affects the peripheral somatosensory system [2]. Spinal cord stimulation (SCS) has been well established as a safe and effective treatment of chronic, intractable pain including neuropathic pain [3,4]. Many studies have indicated that persistent mechanical hypersensitivity was induced in the hind paw following sciatic nerve injuries along with microglial cell accumulation in the spinal dorsal horn (SDH), and the suppression of microglial cell activation in the spinal cord significantly alleviated mechanical hypersensitivity [11,12,13]. In SDH, the increased Iba immunoreactivity that indicates the hyperactive states of microglia was reported to be detected as early as 20 min, peaking on day 3, and remaining at a significant level on day 7 following peripheral nerve injury [14]

Methods

Results

Discussion

Conclusion