Related Experiment Video
Updated: Dec 9, 2025
Combining Peripheral Nerve Grafting and Matrix Modulation to Repair the Injured Rat Spinal Cord
Published on: November 20, 2009
Spinal Cord Stimulation Enhances Microglial Activation in the Spinal Cord of Nerve-Injured Rats
Bin Shu1,2, Shao-Qiu He1, Yun Guan3,4
1Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
Abstract:
Microglia can modulate spinal nociceptive transmission. Yet, their role in spinal cord stimulation (SCS)-induced pain inhibition is unclear. Here, we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury (CCI) of the sciatic nerve. Male rats received conventional SCS (50 Hz, 80% motor threshold, 180 min, 2 sessions/day) or sham stimulation on days 18-20 post-CCI. SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns. SCS also upregulated the mRNAs of M1-like markers, but not M2-like markers. Inducible NOS protein expression was increased, but brain-derived neurotrophic factor was decreased after SCS. Intrathecal minocycline (1 μg-100 μg), which inhibits microglial activation, dose-dependently attenuated the mechanical hypersensitivity. Pretreatment with low-dose minocycline (1 μg, 30 min) prolonged the SCS-induced pain inhibition. These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.
Insights
Spinal cord stimulation (SCS) for pain relief may paradoxically activate M1-like microglia, potentially hindering its own pain-inhibiting effects. Inhibiting microglial activation with minocycline attenuated pain hypersensitivity.
Area of Science:
- Neuroscience
- Pain Research
- Immunology
Background:
- Microglia modulate spinal nociceptive transmission.
- The role of microglia in spinal cord stimulation (SCS)-induced pain inhibition remains unclear.
Purpose of the Study:
- To investigate the effect of SCS on microglial activation in the spinal cord of rats with chronic constriction injury (CCI).
- To determine the impact of microglial activation on SCS-induced pain inhibition.
Main Methods:
- Rats with CCI received conventional SCS or sham stimulation.
- Microglial activation was assessed via OX-42 immunoreactivity and M1/M2 marker expression.
- Mechanical hypersensitivity was measured, and the effect of minocycline on SCS was evaluated.
Main Results:
- SCS transiently reduced mechanical hypersensitivity and increased OX-42 immunoreactivity.
- SCS upregulated M1-like markers but not M2-like markers, increased inducible NOS, and decreased brain-derived neurotrophic factor.
- Minocycline dose-dependently attenuated hypersensitivity and, at low doses, prolonged SCS-induced pain inhibition.
Conclusions:
- Conventional SCS may paradoxically enhance spinal M1-like microglial activity.
- This enhanced microglial activity might compromise SCS's pain-inhibiting efficacy.
- Targeting microglial activation could be a strategy to optimize SCS for pain management.
