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Study Indicates Pain Signals Can be Transmitted from the Peripheral Sensory Nerves to the CNS

pain, model

A research study of GABAergic communication within rodent peripheral sensory ganglia demonstrated that somatosensory pain signals can be transmitted from the peripheral sensory nerves to the central nervous system (CNS). The study further found that necessary proteins required in GABA synthesis were released by sensory neurons and triggered by depolarization. By infusing the sensory ganglia with GABA or GABA reuptake inhibitors, the researchers could significantly reduce or alleviate acute inflammatory or neuropathic pain and nociception in the rodent subjects. They were also able to cause or exacerbate peripherally-induced nociception by GABA-receptor antagonists to sensory ganglia. The study demonstrated that chronic peripheral-induced nociception could be reduced in vivo by chemogenomic or optogenetic depolarization of the GABAergic root ganglion neurons. This indicates a need for further research into peripheral somatosensory ganglia as a potential site of therapeutic pain remediation.

 

Background

Peripheral nerves create pain to convey information to the brain and central nervous symptoms about damage that may be occurring in the body. Healthy nerves send signals from the origin of the impending damage to the spinal cord. There, peripheral somatosensory signals are analyzed within the synapses. It is believed that, prior to their interaction with the spinal cord, nerve fibers do not receive input from the synapses and that cell bodies are unnecessary to the propagation of action potential (AP) to the spinal cord from its periphery. Some chronic pain conditions could be caused or exacerbated by the somatic sensory neurons stimulating peripheral excitation. The researchers involved in this study examined local GABAergic transmission within the DRG to more fully understand why GABA receptors are present in sensory neuron somata and from where any possible activators of the transmitters may originate.

 

Results

In the in vivo study of rodent peripheral sensory ganglia, the researchers’ data determined that GABA is most likely produced in various sub-types of dorsal root ganglion (DRG) neuron. This observation supports the theory that many different sizes and types of DRG neurons may, upon stimulation, be released. In addition, every type of small-diameter DRG neuron may respond to GABA, which satellite glia will remove from the extra satellite space. This release could also signal and set base GABA levels.

Both GABA and the GABA reuptake inhibitor NO711 produce an antinociceptive effect when administered locally in vivo to DRG. When GABA receptor antagonists are similarly delivered, peripherally-induced pain is exacerbated and a nocifensive behavior occurs—even without applied painful stimuli. The results of this observation indicate a healthy endogenous GABAergic inhibition within DRG, though it is still unknown whether the afferent fiber transmission occurs only within the peripheral segments of the DRG.

Previous evidence of cross-excitation within the sensory ganglia and the abundance of neurotransmitter receptors expressed within the somatic and perisomatic sensory neuron sites could point to complex integration of peripheral somatosensory information within the DRG. This study adds a possible new theory of pain to the previously proposed “gate-control” idea.

The research study indicates a potential for the use of focally-applied GABA mimetics or GAT1 inhibitors targeting DRG as a means of pain relief. This idea corresponds with recent studies that concluded that direct stimulation of DRGs through implanted stimulation devices provided relief in people who suffered from neuropathic pain. The authors of this study postulate that the DRG neuromodulation effect works due to the peripheral ganglionic gate and that peripherally-acting GABA mimetics could be used to affect long-term pain relief in pain sufferers.

 

 

 

 

 

Summary
Pain originating from peripheral tissues - a bottom-up perspective
Article Name
Pain originating from peripheral tissues - a bottom-up perspective
Description
pain signals look to be plastic at the dorsal root ganglion suggesting a peripheral pain mechanism origin. This is a study that looks at pain as bottom-up
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Dynamic Disc Designs
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