Abstract
Paresthesia, a common feature of epidural spinal cord stimulation (SCS) for pain management, presents a challenge to the double-blind study design. Although sub-paresthesia SCS has been shown to be effective in alleviating pain, empirical criteria for sub-paresthesia SCS have not been established and its basic mechanisms of action at supraspinal levels are unknown. We tested our hypothesis that sub-paresthesia SCS attenuates behavioral signs of neuropathic pain in a rat model, and modulates pain-related theta (4–8 Hz) power of the electroencephalogram (EEG), a previously validated correlate of spontaneous pain in rodent models. Results show that sub-paresthesia SCS attenuates thermal hyperalgesia and power amplitude in the 3–4 Hz range, consistent with clinical data showing significant yet modest analgesic effects of sub-paresthesia SCS in humans. Therefore, we present evidence for anti-nociceptive effects of sub-paresthesia SCS in a rat model of neuropathic pain and further validate EEG theta power as a reliable ‘biosignature’ of spontaneous pain.
Highlights
Neuropathic pain is highly prevalent, costly and contributes to the opioid crisis[1,2], in part due to ineffective pharmacotherapy and overprescription of opioids[3,4]
In the experiments described below, behavioral and electrophysiological data were recorded in awake rats (n = 9); of these, two rats were excluded from EEG analysis due to electrode failure
Relative to naive (100%), paw withdrawal latencies (PWL) following constriction injury (CCI) significantly decreased to 81.7% ± 3.3 (n = 9 rats), suggesting symptoms of thermal hyperalgesia
Summary
Neuropathic pain is highly prevalent, costly and contributes to the opioid crisis[1,2], in part due to ineffective pharmacotherapy and overprescription of opioids[3,4]. In SCS studies using pre-clinical animal models, current amplitudes are mostly determined under anesthesia in reference to motor thresholds (i.e. minimal current amplitude eliciting muscle twitch), which vary widely between animals and are incompatible with clinical settings whereby SCS protocols are based on the verbal report of paresthesia (i.e. paresthesia-based). To overcome this limitation, we determined paresthesia thresholds in rats according to behaviors indicative of alertness to SCS in awake states. Standard SCS parameters that have been used clinically for over 50 years, while setting the amplitude according to perception threshold (defined as overt behavioral response to the onset of SCS, see Methods)
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