User:OArnold2017/sandbox

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Wide Dynamic Range Neuron[edit]

Gate Control Theory Firing of the inhibitory interneuron (responding to the non-painful stimuli) decreases the probability that the projection neuron (responsible for pain responses) will fire an action potential.

The Wide Dynamic Range (WDR) was first discovered by Mendell in 1966[1]. This neuron is the cell responsible for responses to all types of somatosensory stimuli. They make up the majority of the neurons found in the dorsal horn of the spine, and have the ability to produce long range responses including those responsible for pain and reaction to heat.

Spinal Cord Sectional Anatomy

Anatomy and physiology[edit]

Early studies of the Wide Dynamic Range (WDR) Neuron established in what is known as the Gate Control Theory. The basic concept is that non-painful stimuli block the pathways for painful stimuli, thus inhibiting possible painful responses.[2] This theory was supported by the fact that WDR neurons are responsible for responses to both painful and non-painful stimuli, and the idea that these neurons couldn't produce more than one type of response simultaneously. However, it has since been criticized, with claims that the mechanism is too simple.

WDR neurons are found in the posterior grey column of the spinal cord, with their cell bodies in the posterior horn (dorsal horn). These neurons are primarily responsible for detecting pain and temperature in response to sensory stimuli.

In this area of the spinal cord, there are two different types of neurons responsible for detection of pain- WDR neurons, and Nociceptive Specific (NS) neurons.[3] As the name implies, NS neurons give specific, short range responses.[4] WDR neurons are able to give long range responses for a large variety of stimuli.[3] They work to help identify the location and intensity of painful stimuli.[5]

These neurons differ from most others in that they experience what is called a ‘wind up’. This allows for the intensity of their response to increase with increased frequency of stimuli presentation.[6] Most neurons fire action potentials of the same magnitude as a reaction to a stimulus. The intensity of the stimulus will only increase the frequency of action potentials, not their magnitude. However, WDR neurons exhibit increased action potential intensity with more presentations of a stimulus.[6] This allows for plasticity of the synapse in question[6], and creates flexibility in the neuronal response. Though this may be of some benefit to the organism, this over excitation of the neurons can result in chronic pain.[3]

Role in pain responses[edit]

When there is a painful stimulus there are two pathways that can be taken. The nociceptive neurons in lamina 1 become compromised or the wide dynamic range neurons can become compromised in the dorsal horn of the spinal cord in lamina 5.[7] The wide dynamic range neurons can respond to electrical, mechanical and thermal stimulation.[8] The dorsal cord has faulty plasticity, this allows the development of neuropathic pain after an injury to a nerve. This allows for over-excitation, which can result in chronic pain.[9] Wide dynamic range neurons are also thought to help distinguish the intensity of pain, known as sensory discrimination.[10] The unique pain pathway of the wide dynamic range neurons allows information about the stimulus to be used to map out the intensity of the pain.

There are two main types of pain that we experience in our bodies, pain caused by damage of body tissue and pain caused by nerve damage. Nociceptive pain serves as a warning or signal for tissue damage and works to preserve the body’s equilibrium and functionality. This pain is signaled by the interworking’s of both the peripheral and central nervous systems.[11] Another type of pain which is known as neuropathic pain. This pain is caused by a direct problem or disease that affects the nerves in the central nervous system.[11]

A subset of this neuropathic pain is known as chronic neuropathic pain which is characterized by its long lasting and high pain intensity. Although there is still a lot unknown about the direct cause of this chronic pain, it has been linked to wide dynamic range neurons. Wide dynamic range neurons, which are located in the spinal cord, show significant activation by sympathetic stimulation while neurons such as nociceptor-specific did not show the same level of activation.[12] The blocking of sympathetic pathways seemed to decrease pain and once unblocked, symptoms of pain persisted. This indicates that one of the many complex mechanisms contributing to this neuropathic chronic pain is the overstimulation of the wide dynamic neurons in the dorsal horn by sympathetic stimulation.[11] Another aspect that plays a role in neuropathic pain is the transient receptor channel called TRPA1. This channel is known to have influenced chronic pain injuries and diseases such as inflammation, diabetes, fibromyalgia, bronchitis, and emphysema.[13] Wide dynamic neurons are a huge part of the somatosensory system, and helps send and receive signals based on sensory changes in the body. The TRPA1 channel has been closely associated with temperature and pain sensation in primary afferent sensory neurons and are largely found in nociceptive sensory neurons in the dorsal root ganglia.[14] The inhibition of TRPA1 is known to contribute to different inflammatory and neuropathic diseases by amplifying the pain and hypersensitivity.[13] This is an area of study that is beneficial to continue to study and learn how to target and control aspects of chronic inflammatory and neuropathic diseases involved in sensory responses that wide dynamic range neurons play a role in.

Role in itch responses[edit]

Additionally, the itch pathway has also been linked with wide dynamic range neurons because itch and pain pathways are closely associated. Brain imaging indicates similar activity in many areas of the brain such as prefrontal, supplementary motor areas, premotor cortex, anterior insular cortex, and many others when itch and pain regions are activated.[14] A better understanding of both these pathways will provide a greater understanding of wide dynamic range neurons.

  1. ^ Mendell, L. M. (1966-11-01). "Physiological properties of unmyelinated fiber projection to the spinal cord". Experimental Neurology. 16 (3): 316–332. doi:10.1016/0014-4886(66)90068-9. ISSN 0014-4886. PMID 5928985.
  2. ^ Meyerson, Björn A.; Linderoth, Bengt (2006-04-01). "Mode of action of spinal cord stimulation in neuropathic pain". Journal of Pain and Symptom Management. 31 (4 Suppl): S6–12. doi:10.1016/j.jpainsymman.2005.12.009. ISSN 0885-3924. PMID 16647596.
  3. ^ a b c Zhang, Tianhe C.; Janik, John J.; Grill, Warren M. (2014-06-20). "Mechanisms and models of spinal cord stimulation for the treatment of neuropathic pain". Brain Research. 1569: 19–31. doi:10.1016/j.brainres.2014.04.039. PMID 24802658. S2CID 377729.
  4. ^ West, S. J.; Bannister, K.; Dickenson, A. H.; Bennett, D. L. (2015-08-06). "Circuitry and plasticity of the dorsal horn – Toward a better understanding of neuropathic pain". Neuroscience. 300: 254–275. doi:10.1016/j.neuroscience.2015.05.020. PMID 25987204. S2CID 5368944.
  5. ^ Craig, A.D. (March 6, 2003). "Pain Mechanisms: Labeled Lines Versus Convergence in Central Processing". Annual Review of Neuroscience. 26: 1–30. doi:10.1146/annurev.neuro.26.041002.131022. PMID 12651967. Retrieved March 16, 2017.
  6. ^ a b c D'Mello, R.; Dickenson, A. H. (2008-07-01). "Spinal cord mechanisms of pain". British Journal of Anaesthesia. 101 (1): 8–16. doi:10.1093/bja/aen088. ISSN 0007-0912. PMID 18417503.
  7. ^ Inui, Koji (2012-11-01). "[Pain pathway]". Brain and Nerve = Shinkei Kenkyu No Shinpo. 64 (11): 1215–1224. ISSN 1881-6096. PMID 23131731.
  8. ^ Lynn, R. B. (1992-05-27). "Mechanisms of esophageal pain". The American Journal of Medicine. 92 (5A): 11S–19S. doi:10.1016/0002-9343(92)80051-z. ISSN 0002-9343. PMID 1595755.
  9. ^ West, S. J.; Bannister, K.; Dickenson, A. H.; Bennett, D. L. (2015-08-06). "Circuitry and plasticity of the dorsal horn--toward a better understanding of neuropathic pain". Neuroscience. 300: 254–275. doi:10.1016/j.neuroscience.2015.05.020. ISSN 1873-7544. PMID 25987204. S2CID 5368944.
  10. ^ Mertens, P.; Blond, S.; David, R.; Rigoard, P. (2015-03-01). "Anatomy, physiology and neurobiology of the nociception: a focus on low back pain (part A)". Neuro-Chirurgie. 61 Suppl 1: S22–34. doi:10.1016/j.neuchi.2014.09.001. ISSN 1773-0619. PMID 25441598.
  11. ^ a b c "Mechanisms of neuropathic pain". www.sciencedirect.com. Retrieved 2017-03-27.
  12. ^ Roberts, W. J.; Foglesong, M. E. (1988-09-01). "Spinal recordings suggest that wide-dynamic-range neurons mediate sympathetically maintained pain". Pain. 34 (3): 289–304. doi:10.1016/0304-3959(88)90125-X. ISSN 0304-3959. PMID 3186277. S2CID 32428131.
  13. ^ a b Garrison, Sheldon R.; Stucky, Cheryl L. (2017-03-27). "The Dynamic TRPA1 Channel: A Suitable Pharmacological Pain Target?". Current Pharmaceutical Biotechnology. 12 (10): 1689–1697. doi:10.2174/138920111798357302. ISSN 1389-2010. PMC 3884818. PMID 21466445.
  14. ^ a b Akiyama, Tasuku; Carstens, E. (2013-10-10). "Neural processing of itch". Neuroscience. 250: 697–714. doi:10.1016/j.neuroscience.2013.07.035. ISSN 0306-4522. PMC 3772667. PMID 23891755.
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