An Electroencephalography Bioassay for Preclinical Testing of Analgesic Efficacy

Abstract

We present a multimodal method combining quantitative electroencephalography (EEG), behavior and pharmacology for pre-clinical screening of analgesic efficacy in vivo. The method consists of an objective and non-invasive approach for realtime assessment of spontaneous nociceptive states based on EEG recordings of theta power over primary somatosensory cortex in awake rats. Three drugs were chosen: (1) pregabalin, a CNS-acting calcium channel inhibitor; (2) EMA 401, a PNS-acting angiotensin II type 2 receptor inhibitor; and (3) minocycline, a CNS-acting glial inhibitor. Optimal doses were determined based on pharmacokinetic studies and/or published data. The effects of these drugs at single or multiple doses were tested on the attenuation of theta power and paw withdrawal latency (PWL) in a rat model of neuropathic pain. We report mostly parallel trends in the reversal of theta power and PWL in response to administration of pregabalin and EMA 401, but not minocycline. We also note divergent trends at non-optimal doses and following prolonged drug administration, suggesting that EEG theta power can be used to detect false positive and false negative outcomes of the withdrawal reflex behavior, and yielding novel insights into the analgesic effects of these drugs on spontaneous nociceptive states in rats.

Time-dynamic pulse modulation of spinal cord stimulation reduces mechanical hypersensitivity and spontaneous pain in rats

“…2a, left panel), paw withdrawal threshold in the hind paw ipsilateral to CCI decreased significantly to 5.93 ± 0.76 g compared to baseline 11.58 ± 0.54 g (p = 0.0002, n = 8 rats), suggesting successful reproduction of the model. Previous studies from our laboratory demonstrated that spontaneous pain in rats following CCI correlates reliably with enhanced EEG theta (4-8 Hz) power in the contralateral S1 21,23,24 . In this study, results also suggest ( Fig.…”

“…EEG implant. As described previously 23,24,46 , the head was fixed in a stereotaxic apparatus, and the skull was exposed after a small midline skin incision. A stainless-steel screw electrode (0-80 ga 1/8-inch, impedance = 0.6 www.nature.com/scientificreports/ Ω; component Supply Company, Fort Meade, FL) was placed over the intact skull (i.e.…”

“…The SCS patterns evaluated included five categories: (A) Tonic (conventional); (B) Amplitude Modulation; (C) Pulse Width Modulation; (D) Sinusoidal Rate Modulation; and (E) Stochastic Rate Modulation. The strengths of our approach include the use of two outcome measures of pain in rodents, the paw withdrawal threshold (mechanical hypersensitivity) and resting state EEG power in the theta (4)(5)(6)(7)(8) band (a biomarker of spontaneous pain [21][22][23][24] ), a custom-made SCS lead for rats, and a longitudinal, randomized, double-blind, and crossover experimental design. Our data demonstrate that under the parameter settings used in this study, all the TDP patterns evaluated except pulse width modulation significantly reversed mechanical hypersensitivity.…”

EEG individual power profiles correlate with tension along spine in horses

“…However most behavioural or even imagery paradigms (i.e. grimace scales, conditioned place preference, burrowing, brain imaging) proposed lately may be too subjective or lack the necessary temporal resolution to respond to these criteria [3].…”

A controlled thermoalgesic stimulation device to identify novel pain perception biomarkers

“…Here we have asked whether pain perception might be encoded through different physiological signals and we sought to assess their possible interactions. The physiological response to pain has been addressed previously using approaches like EEG [6], [7] and PPG [8], [9], yet these signals are typically analyzed separately. Moreover, the paradigm to produce painful stimulation relies on human intervention [10] or environmental factors [11], which may compromise the reliability of these results.…”