The Role Of Opioid ? Receptors On Different Types Of Cells In Stress Analgesia

The pain protects the body and allows the body to escape harmful stimuli.Paralgesia can induce various adverse reactions,such as chronic paralgesia(e.g.,pathological neuralgia)can induce emotional reactions,psychological and mental problems(e.g.,anxiety,depression,etc.).Stress is a common cause of paralgesia,which leads to mood disorders.It is usually characterized by hyperalgesia and algesthesia.Algesthesia is the primary stage for developing hyperalgesia.The endogenous pain inhibitory systems can be activated by stress.It is well documented that stress activates different intrinsic pain inhibitory mechanisms,leading to analgesia in humans and antinociception in rodents,a phenomenon referred to as stress-induced analgesia(SIA).The analgesic effect induced by emotional response is mainly through activation of the descending inhibition system,thereby inhibiting the transmission of pain.The researchers proposed an endogenous analgesia feedback loop consisting of the spinal cord-thalamic nucleus submedius(Sm)-ventrolateral orbital cortex(VLO)-periaqueductal gray(PAG)-spinal cord,which leads to activation of the PAG-brainstem descending inhibitory system and depression of the nociceptive inputs in the spinal cord and trigeminal nucleus.In this analgesic system,neurotransmitters or neuropeptides such as serotonin,dopamine,glutamic acid,?-aminobutyric acid,endocannabinoids and their corresponding receptors play a regulatory role,in which the role of endogenous opioid system is particularly prominent in SI A.Opioid receptors are widely expressed in central pain transmission systems,the research used mu-opioid receptors(?Rs)cell-specific gene knockout techniques to investigate the contribution of ?Rs expressed on different cells in SIA.Previous researches have shown that ?Rs in VLO are involved in analgesia,this experiment is to further explore the role of ?Rs expressed on different cells in VLO in SIA.The main results are as follows:(1)Establishment of SIA modelThe pain threshold of the mice was measured with a YLS-12A mouse tail light pain meter.The pain threshold was expressed by Tail Flick Latency(TFL),and the TFL of the mice was measured before and after the footshock.The result showed that the TFL at each time point of measurements after footshock was significantly different from the baseline value.The pain threshold increased within 0-25 min after the footshock,indicating that the footshock caused an analgesic effect.(2)The effect of opioid receptors on SIAThe role of opioid receptors in SIA was initially determined by intraperitoneal injection of the opioid receptors antagonist Naloxone(10 mg/kg).The result showed that there was a significant difference between the naloxone group and the saline group.SIA was attenuated after injection of Naloxone.(3)The effect of ?Rs expressed on different cells on SIAThe result of knockout mice showed that systemic knockout of ?Rs can attenuate SIA,which is consistent with the result of intraperitoneal injection of Naloxone,indicating that ?Rs is involved in SIA.Specific knockout of ?Rs on GABAergic neurons and astrocytes can attenuate SIA,but specific knockout of ?Rs on glutamatergic neurons has no effect on SIA.(4)The effect of ?Rs in VLO on SIAThe role of ?Rs in SIA was initially determined by microinjection of the ?Rs antagonist CTAP(0.5 ?g/?L)in VLO.The result showed that there was a significant difference between the CTAP group and the saline group.SIA was attenuated after injection of CTAP,indicating that ?Rs in VLO was involved in the regulation of SIA.(5)The effect of ?Rs expressed on different cells in VLO on SIAThe ?Rs on GABAergic neurons in VLO can regulate SIA.The ?Rs on glutamatergic neurons and astrocytes have no effect on the regulation of SIA.In summary,?Rs on GABAergic neurons and astrocytes were involved in the regulation of SIA.Further investigation revealed that ?Rs expressed on GABAergic neurons in VLO were involved in the regulation of SIA.