BDNF-trkB-KCC2-GABA pathway may be related to chronic stress-induced hyperalgesia at both the spinal and supraspinal level.

Chronic stresses can induce physiological and psychological changes and result in stress-related neuropsychiatry, sometimes they may also contribute to hypersensitivity to pain known as stress-induced hyperalgesia (SIH). Recently it was found that GABAergic disinhibition is closely related to morphine and chronic inflammation pain induced hyperalgesia in the PAG (periaqueductal gray)-RVM (rostral ventromedial medulla) -spinal descending facilitatory system, the changes of potassium-chloride co-transporter 2 (KCC2) function or expression modulated by brain-derived neurotrophic factor (BDNF) are involved in it. Similarly, chronic stress could induce changes of BDNF, KCC2 and a depolarizing shift in the GABA reversal potential (EGABA). Moreover, the descending facilitatory system has been suggested to be related with SIH, but whether it modulates SIH through disinhibition by the downregulation of KCC2 expression and/or transport function remains unknown. We therefore hypothesized that SIH may be owned to disinhibition caused by the activation of BDNF-trkB-KCC2-GABA pathway, which would provide a new understanding for SIH.