Abstract
Mechanisms underlying remifentanil- (RF-) induced hyperalgesia, a phenomenon that is generally named as opioid-induced hyperalgesia (OIH), still remain elusive. The ventral posterior lateral nucleus (VPL) of the thalamus, a key relay station for the transmission of nociceptive information to the cerebral cortex, is activated by RF infusion. Electroacupuncture (EA) is an effective method for the treatment of pain. This study aimed to explore the role of VPL in the development of OIH and the effect of EA treatment on OIH in rats. RF was administered to rats via the tail vein for OIH induction. Paw withdrawal threshold (PWT) in response to mechanical stimuli and paw withdrawal latency (PWL) to thermal stimulation were tested in rats for the assessment of mechanical allodynia and thermal hyperalgesia, respectively. Spontaneous neuronal activity and local field potential (LFP) in VPL were recorded in freely moving rats using the in vivo multichannel recording technique. EA at 2 Hz frequency (pulse width 0.6 ms, 1–3 mA) was applied to the bilateral acupoints “Zusanli” (ST.36) and “Sanyinjiao” (SP.6) in rats. The results showed that both the PWT and PWL were significantly decreased after RF infusion to rats. Meanwhile, both the spontaneous neuronal firing rate and the theta band oscillation in VPL LFP were increased on day 3 post-RF infusion, indicating that the VPL may promote the development of RF-induced hyperalgesia by regulating the pain-related cortical activity. Moreover, 2 Hz-EA reversed the RF-induced decrease both in PWT and PWL of rats and also abrogated the RF-induced augmentation of the spontaneous neuronal activity and the power spectral density (PSD) of the theta band oscillation in VPL LFP. These results suggested that 2 Hz-EA attenuates the remifentanil-induced hyperalgesia via reducing the excitability of VPL neurons and the low-frequency (theta band) oscillation in VPL LFP.
Highlights
As an ideal ultrashort-acting opioid, remifentanil (RF) is widely used in clinical anesthesia
We found that both the excitability of ventral posterior lateral nucleus (VPL) neurons and the activity of theta band power spectral density (PSD) in VPL local field potential (LFP) are increased after RF infusion, indicating that the VPL may promote the development of RF-induced hyperalgesia by regulating the pain-related cortical activity
To investigate the ongoing neuronal activity in the VPL associated with RF-induced hyperalgesia, we examined the changes in mean spontaneous firing rate of VPL neurons by in vivo multichannel recording in free-moving rats
Summary
As an ideal ultrashort-acting opioid, remifentanil (RF) is widely used in clinical anesthesia. The clinical symptoms of OIH are manifested as an increased sensitivity to noxious stimuli, and preclinical experiments have shown that mechanical and thermal hyperalgesia appeared after RF withdrawal [1,2,3]. In rats with central pain after spinal cord injury, neurons in the VPL firing spontaneously at a high rate, with increased after-discharges and evoked responses [9]. Both preclinical and clinical studies have found that VPL and other brain regions can be activated by RF [10,11,12]. We first investigated the role of VPL in the development of OIH by in vivo multichannel recording in this study
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