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What are the most common causes of chronic pain treated by neuromodulation? 

Neuromodulation (medicine)
Nociceptor
Dorsal root ganglion
Neuroma
GABAergic
Best insight from top research papers

Chronic pain, a complex and multifaceted condition, can arise from various sources, many of which are amenable to treatment through neuromodulation techniques. One common cause is inflammatory diseases and neuropathic insults, which can lead to severe and often treatment-resistant pain due to a loss of synaptic inhibition in the spinal dorsal horn. This type of pain can be exacerbated by changes in GABA neurotransmission in the rostral agranular insular cortex, affecting the pain threshold and potentially leading to analgesia or hyperalgesia. Additionally, peripheral nerve injury can result in a disruption of anion homeostasis in neurons, causing inhibitory synaptic currents to become excitatory and contributing to neuropathic pain. Neuronal plasticity, or the brain's ability to change in response to experience, is another significant contributor to chronic conditions like tinnitus, which shares underlying mechanisms with chronic pain. Trauma to peripheral nerves may also lead to chronic pain syndromes, with abnormal discharge originating within the dorsal root ganglia as a potential source. Furthermore, the activation of P2X receptors on dorsal root ganglion neurons can modify sensory signal throughput, influencing pain sensation. The role of neurotransmitter mobilization in nerve endings, which can affect the transmission effectiveness, is another aspect to consider in the context of chronic pain. The activation of NMDA receptors in the spinal cord, leading to the release of substance P and subsequent pain and morphological changes in dorsal horn neurons, highlights the complexity of pain signaling pathways. Lastly, damaged nerves that become spontaneously active can serve as impulse generators, contributing to the pain experience. Neuromodulation techniques, by targeting these various mechanisms, offer hope for managing chronic pain arising from these diverse causes.

Answers from top 10 papers

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Papers (10)Insight
Journal Article•DOI
Properties of afferent nerve impulses originating from a neuroma.
Patrick D. Wall, Patrick D. Wall, Michael J. Gutnick 
26 Apr 1974-Nature
387 Citations
Not addressed in the paper.
Journal Article•DOI
Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses.
Jianguo G. Gu, Amy B. MacDermott 
16 Oct 1997-Nature
493 Citations
Not addressed in the paper.
Journal Article•DOI
NMDA-receptor regulation of substance P release from primary afferent nociceptors
Hantao Liu, Patrick W. Mantyh, Allan I. Basbaum 
17 Apr 1997-Nature
427 Citations
Not addressed in the paper.
Journal Article•DOI
Repetitive activation of motor nerve endings.
John I. Hubbard, Robert F. Schmidt 
27 Oct 1962-Nature
10 Citations
Not addressed in the paper.
Open access•Journal Article•DOI
A wireless closed-loop system for optogenetic peripheral neuromodulation
Aaron D. Mickle, Sang Min Won, Kyung Nim Noh, Jangyeol Yoon, Kathleen Meacham, Yeguang Xue, Lisa A. McIlvried, Bryan A. Copits, Vijay K. Samineni, Kaitlyn E. Crawford, Do Hoon Kim, Paulome Srivastava, Bong Hoon Kim, Bong Hoon Kim, Seunghwan Min, Young Shiuan, Yeojeong Yun, Maria A. Payne, Jianpeng Zhang, Hokyung Jang, Yuhang Li, H. Henry Lai, H. Henry Lai, Yonggang Huang, Sung Il Park, Robert W. Gereau, John A. Rogers 
02 Jan 2019-Nature
301 Citations
Neuromodulation commonly treats chronic pain from conditions like overactive bladder, urinary incontinence, and interstitial cystitis by stimulating the peripheral nervous system with bioelectronic implants.
Open access•Journal Article•DOI
Reversing pathological neural activity using targeted plasticity
Jonathan Riley, Jonathan D. Seale, William A. Vrana, Jai Shetake, Sindhu P. Sudanagunta, Michael S. Borland, Michael P. Kilgard 
03 Feb 2011-Nature
578 Citations
Not addressed in the paper.
Journal Article•DOI
Reversal of pathological pain through specific spinal GABAA receptor subtypes.
Julia Knabl, Robert Witschi, Katharina Hösl, Heiko Reinold, Ulrike B. Zeilhofer, Seifollah Ahmadi, Seifollah Ahmadi, Johannes Brockhaus, Johannes Brockhaus, Marina Sergejeva, Andreas Hess, Kay Brune, Jean-Marc Fritschy, Uwe Rudolph, Uwe Rudolph, Hanns Möhler, Hanns Möhler, Hanns Ulrich Zeilhofer, Hanns Ulrich Zeilhofer, Hanns Ulrich Zeilhofer 
17 Jan 2008-Nature
402 Citations
Not addressed in the paper.
Journal Article•DOI
Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex.
Luc Jasmin, Samuel D. Rabkin, Alberto Granato, Abdennacer Boudah, Peter T. Ohara 
17 Jul 2003-Nature
315 Citations
Not addressed in the paper.
Journal Article•DOI
Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain
Jeffrey A. M. Coull, Dominic Boudreau, Karine Bachand, Steven A. Prescott, Steven A. Prescott, Francine Nault, Francine Nault, Attila Sik, Paul De Koninck, Yves De Koninck, Yves De Koninck 
21 Aug 2003-Nature
1K Citations
Not addressed in the paper.
Journal Article•DOI
Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia
Elspeth M. McLachlan, Wilfrid Jänig, Marshall Devor, Martin Michaelis 
10 Jun 1993-Nature
711 Citations
Not addressed in the paper.

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