Anti-interleukin-6 receptor antibody reduces neuropathic pain following spinal cord injury in mice

Abstract

The present study reports the beneficial effects of an anti-mouse interleukin-6 (IL-6) receptor antibody (MR16-1) on neuropathic pain in mice with spinal cord injury (SCI). Following laminectomy, contusion SCI models were produced using an Infinite Horizon (IH)-impactor. MR16-1 was continuously injected for 14 days using Alzet osmotic pumps. A mouse IL-6 ELISA kit was then used to analyze IL-6 levels in the spinal cord tissue between 12 and 72 h after injury. Motor and sensory functions were evaluated each week using the Basso Mouse Scale (BMS), plantar von Frey and thermal threshold tests. Histological examinations were performed 42 days after SCI. Between 24 and 72 h after SCI, the expression levels of IL-6 were significantly decreased in the MR16-1 treated group. Six weeks after surgery, the BMS score of the MR16-1-treated group indicated significant recovery of neurological functions. MR16-1-treated mice in the SCI group exhibited lower paw withdrawal thresholds in the plantar von Frey and thermal tests, which were used to evaluate allodynia. MR16-1 treatment significantly increased the area of Luxol fast blue-stained tissue, representing spared myelin sheaths. These results indicate that the continuous inhibition of IL-6 signaling by MR16-1 between the early and sub-acute phases following SCI leads to neurological recovery and the suppression of hyperalgesia and allodynia. Overall, our data suggest that the inhibition of severe inflammation may be a promising neuroprotective approach to limit secondary injury following SCI and that an anti-IL-6 receptor antibody may have clinical potential for the treatment of SCI.

The non-psychoactive phytocannabinoid cannabidiol (CBD) attenuates pro-inflammatory mediators, T cell infiltration, and thermal sensitivity following spinal cord injury in mice

“…For example, Hoschouer et al 2009 reported no changes in mechanical sensitivity following contusion injury to the thoracic region, while Chen et al 2012 reported tactile allodynia in their model[40, 41]. Moreover, insensitivity has been reported at early time points and hypersensitivity at later time points, and hypersensitivity to thin filaments but hyposensitivity to thicker filaments[42, 43]. Taken together the presence and direction of tactile changes following spinal contusion injury in mice is variable across laboratories and likely relates to the level and nature of damage to the dorsal column pathway transmitting ascending mechanical touch information.…”

Developmental Changes in Pain and Spinal Immune Gene Expression after Radicular Trauma in the Rat

“…Nerve injury upregulates IL-6 and reduction of IL-6 reduces neuropathic pain (65, 69, 70). It has been proposed that TNFα upregulates IL-6 expression via a NF-κB pathway (71).…”

Differential Association Between Biomarkers of Subclinical Inflammation and Painful Polyneuropathy: Results From the KORA F4 Study

“…Interestingly, there is evidence from a mouse model that the inhibition of IL-6 activity with a monoclonal antibody against IL-6R reduces neuropathic pain (19). On one hand, it remains to be elucidated whether intracellular signaling downstream of the IL-6R/gp130 complex (e.g., by activation of the transcription factors Janus kinase and signal transducer and activator of transcription (20)) contribute to the development of neuropathic pain.…”