Decreased intracellular GABA levels contribute to spinal cord stimulation-induced analgesia in rats suffering from painful peripheral neuropathy: The role of KCC2 and GABAA receptor-mediated inhibition

Spinal Cord Stimulation Reduces Mechanical Hyperalgesia and Restores Physical Activity Levels in Animals with Noninflammatory Muscle Pain in a Frequency-Dependent Manner

“…The effects of SCS at higher frequencies are similar to that found in animals with nerve injury. 13,14,[18][19][20]22,23,28,67,76 However, our previous studies show that a lower frequency (4 Hz) also reduced nerve injury-induced pain. 67,69,77 The differences between sensitivity to low-and high-frequency SCS between the models is unclear but could relate to different mechanisms of action of low-and high-frequency SCS, since low-frequency (4 Hz) SCS uses μ-opioid receptors and high-frequency (60 Hz) SCS uses δ-opioid receptors.…”

“…Some studies show a cumulative and long-lasting (carryover) effect with repeated SCS, 67,68,81 while others show a more short-term effect that lasts for minutes or hours after SCS. 14,23,69,82,83 It is possible that the differences between studies relates to variables of stimulation. Previous studies have routinely delivered SCS at amplitudes of 60% to 70% of motor threshold, 14,23,83 which is similar to that used clinically.…”

“…14,23,69,82,83 It is possible that the differences between studies relates to variables of stimulation. Previous studies have routinely delivered SCS at amplitudes of 60% to 70% of motor threshold, 14,23,83 which is similar to that used clinically. However, the current study delivered SCS at a higher amplitude, 90% motor threshold.…”

“…98,99 Indeed SCS reduces sensitivity of dorsal horn neurons to noxious stimuli, 76 activates local and descending inhibitory pathways from the brainstem, 17,21,77 and uses the inhibitory neurotransmitters γ-aminobutyric acid, serotonin, and opioids to produce analgesia. [18][19][20][21][22][23][24][25][26][27][28] In addition, both 4 and 60 Hz SCS, in part, work through opioid receptor mechanisms, with 4 Hz SCS activating μ-opioid receptors while 60 Hz SCS activates δ-opioid receptors. 69 Thus, the ability of SCS to reduce hyperalgesia in a model of noninflammatory muscle pain could be related to its ability to restore neurochemical balance in the central pathways by reducing excitation and increasing inhibition.…”

Burst and Tonic Spinal Cord Stimulation Differentially Activate GABAergic Mechanisms to Attenuate Pain in a Rat Model of Cervical Radiculopathy

“…Quantifying intracellular and extracellular GABA concentrations in the dorsal horn would provide a more direct measurement of GABA signaling and dysfunction in the spinal cord [44], [45]. However, the changes in serum GABA levels in this study [see Fig.…”