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iNature
Refentanil-induced hyperalgesia (RIH) is a serious but common postoperative clinical problem whose underlying neural mechanisms are elusive
.
On December 15, 2022, Tao Wenjuan of Anhui Medical University and Zhang Zhi of University of Science and Technology of China jointly published a joint newsletter entitled "Thalamocortical circuits drive remifentanil-induced" online in the Journal of Clinical Investigation (IF=19).
Postoperative Hyperalgesia", which showed that the thalamic cortical circuits drive refentanil-induced postoperative hyperalgesia
.
The study found that glutamate neurons in the ventrolateral posterolateral nucleus of the thalamus (VPLGlu) showed significantly elevated explosive firing in RIH model mice, accompanied by upregulation
of Ca v 3.
1 T-type calcium channel expression and function.
In addition, the study identified a glutamatergic neuronal thalamic cortical circuit in the VPL that projects into the hindlimb primary somatosensory cortex glutamatergic neurons (S1HLGlu), mediating RIH
.
In vivo calcium imaging and multipole electrode recordings showed enhanced S1HLGlu neuronal activity during RIH
.
In addition, preoperative inhibition of Cav3.
1-dependent burst firing in VPL Glu neurons or chemogenesis inhibition ofVPLGlu neuronal terminals in S1HL eliminated increased S1HLGlu neuronal excitability while mitigating RIH
.
In conclusion, the results suggest that remifentanil activates S1HL Glu neurons by upregulating T-type calcium channel-dependent explosive firing in VPLGlu neurons, thereby inducing postoperative hyperalgesia, thereby revealing the basis of ion channel-mediated RIH neural circuits that can guide the development of
analgesia.
In addition, on July 7, 2022, Zhang Zhi of the University of Science and Technology of China, Tao Wenjuan of Anhui Medical University, and Liu Yuanyuan of the National Institute of Health (NIH) jointly published a joint newsletter entitled "Sound induces analgesia through corticothalamic circuits" on Science Online The study paper found that the analgesic effect of sound depended on a low (5 dB) signal-to-noise ratio (SNR)
relative to ambient noise in mice.
Viral tracking, microendoscopic calcium imaging, and multipolar recordings in free-moving mice showed that low signal-to-noise ratio sound inhibits glutamatergic input
from the auditory cortex (ACxGlu) to the posterior thalamic nucleus (PO) and posterior abdominal nuclei (VP).
Optogenetic or chemogenetic suppression of the ACx Glu→PO and ACxGlu→VP circuits mimics the analgesia induced by low SNR sounds in the inflamed hind paws and front paws, respectively
.
Artificial activation of these two circuits eliminates sound-induced analgesia
.
In conclusion, the study revealed the cortical thalamic circuitry behind sound-promoting analgesia by deciphering the role of the auditory system in pain management (click to read).
.
However, its use as a potent agonist of μ-opioid receptors (MORs) has long been associated with
the development of remifentanil-induced hyperalgesia (RIH).
Paradoxically, patients who use opioids to control pain during surgery may exhibit enhanced postoperative sensitivity
to painful stimuli.
Both clinical and preclinical animal model studies have shown that refentanil treatment produces and enhances sensitivity to postoperative pain, with increased pain intensity, increased opioid consumption, and worsening
adverse opioid side effects.
In addition to these problems, acute pain that is not effectively controlled can also become chronic
.
Due to the urgent clinical need for strategies to prevent and treat RIH, research attention is increasingly focused on
identifying its underlying mechanisms.
It is well known that thalamic cortical circuits within the central nervous system are necessary to discern the location, intensity, and quality of noxious stimuli and play a key role
in the perception of pain.
The ventral posterolateral nucleus (VPL) is a higher-order thalamic cortex structure that is a somatosensory channel
that distributes pain information from the acanthocious tract to the appropriate circuits in the cerebral cortex.
VPL mainly contains glutamate neurons, which exhibit prominent tense and explosive firing patterns
.
Explosive firing is a unique pattern of neuronal firing activity that occurs in the thalamus and plays an important role
in pain signaling.
Neuronal burst firing is mediated by T-type calcium 3.
1 (Cav3.
1) channels, which are highly expressed subtypes
of low-pressure-activated T-type calcium channels in hypothemus-projected neurons in the thalamic cortex.
In animal models,Cav3.
1 knockout can attenuate spontaneous and mechanical pain in mice with spinal cord neuropathic pain or trigeminal neuropathic pain, which together suggests that Cav3.
1channel dysfunction may lead to abnormal thalamic cortical dynamics
associated with chronic pain neuropathy.
Based on these findings, next, it is necessary to determine how the spike pattern of VPL neurons changes during RIH and how the Cav3.
1 channel promotes the activity of RIH thalamic cortical circuits
.
In summary, the author's study shows that VPL Glu → S1HL Glu pathway is involved in the occurrence of RIH, which is VPL Glu caused by the imbalance of theCa v3.
1 channel Overactive explosive firing
of neurons.
In conclusion, the results provide a novel RIH molecular and circuit mechanism, suggesting that T-channel blockers may be an effective way
to prevent postoperative hyperalgesia.
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The content is [iNature]
