Editing Chronic pain (section)

== Etiology ==
Chronic pain has many [[Pathophysiology|pathophysiological]] and environmental causes and can occur in cases such as [[Peripheral neuropathy|neuropathy]] of the central nervous system, after cerebral hemorrhage, tissue damage such as extensive burns, inflammation, autoimmune disorders such as rheumatoid arthritis, psychological stress such as headache, migraine or abdominal pain (caused by emotional, psychological or behavioral) and mechanical pain caused by tissue wear and tear such as arthritis.<ref name="Dydyk-2023">{{Cite journal|last1=Dydyk|first1=Alexander M|last2=Till|first2=Conermann|date=June 2023|editor-last=Abrazo Central Campus|title=Chronic Pain|url=https://www.ncbi.nlm.nih.gov/books/NBK553030/|journal=StatPearls [Internet]|publisher=StatPearls Publishing|pmid=31971706|archive-date=2024-03-06|access-date=2024-01-24|archive-url=https://web.archive.org/web/20240306101622/https://www.ncbi.nlm.nih.gov/books/NBK553030/|url-status=live}}</ref> In some cases, chronic pain can be caused by genetic factors which interfere with neuronal differentiation, leading to a permanently lowered threshold for pain.<ref>{{cite journal |vauthors=Rusanescu G, Mao J |date=October 2014 |title=Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord |journal=Journal of Cellular and Molecular Medicine |volume=18 |issue=10 |pages=2103–16 |doi=10.1111/jcmm.12362 |pmc=4244024 |pmid=25164209}}</ref>

The pathophysiological [[etiology]] of chronic pain remains unclear. Many theories of chronic pain<ref>{{cite journal |vauthors=((Apkarian, A. V.)), ((Baliki, M. N.)), ((Geha, P. Y.)) |date=February 2009 |title=Towards a theory of chronic pain |journal=Progress in Neurobiology |volume=87 |issue=2 |pages=81–97 |doi=10.1016/j.pneurobio.2008.09.018 |pmc=2650821 |pmid=18952143}}</ref><ref>{{cite book |title=Sciatica and Chronic Pain |vauthors=((Baloh, R. W.)) |date=2019 |publisher=Springer International Publishing |isbn=978-3-319-93903-2 |pages=71–88 |chapter=Why does pain persist in so many cases? |doi=10.1007/978-3-319-93904-9_7 |s2cid=56824408}}</ref> fail to clearly explain why the same pathological conditions do not invariably result in chronic pain. Patients' anatomical predisposition to proximal neural compression (in particular of peripheral nerves) may be the answer to this conundrum. Proximal neural lesion at the level of the [[dorsal root ganglion]] (DRG) may drive a [https://www.frontiersin.org/files/Articles/1037376/fpain-04-1037376-HTML-r1/image_m/fpain-04-1037376-g002.jpg vicious cycle of chronic pain] by causing postural protection of the painful site and consequent neural compression in the same spinal region. Difficulties in diagnosing proximal neural lesion<ref>{{Cite journal |last1=Hendler |first1=N.H. |last2=Kozikowski |first2=J.G. |date=November 1993 |title=Overlooked Physical Diagnoses in Chronic Pain Patients Involved in Litigation |url=https://linkinghub.elsevier.com/retrieve/pii/S003331829371823X |journal=Psychosomatics |language=en |volume=34 |issue=6 |pages=494–501 |doi=10.1016/S0033-3182(93)71823-X|pmid=8284339 }}</ref> may account for the theoretical perplexity of chronic pain.

=== Pathophysiology ===
[[File:Discogenic Pain.png|thumb|Continuous pressure on the spine can destroy the [[intervertebral disc]] and cause the [[sciatic nerve]] to actively produce pain.]]
The mechanism of continuous activation and transmission of pain messages, leads the body to an activity to relieve pain (a [[Mechanism (biology)|mechanism]] to prevent damage in the body), this action causes the release of [[prostaglandin]] and increase the sensitivity of that part to [[stimulation]]; Prostaglandin secretion causes unbearable and chronic pain.<ref name="Panahi-2018">{{Cite book |last1=Neuroscience |first1=Association |title=Brain facts |last2=Panahi |first2=Reza |last3=Soor |first3=Behnam |last4=Shahbazi |first4=Ali |last5=Haqparest |first5=Abbas |date=2018 |publisher=Satish Hasti Publishing House |isbn=978-622-6445-63-4 |location=Tehran.Iran |page=113}}</ref> Under persistent activation, the transmission of pain signals to the [[Posterior horn of spinal cord|dorsal horn]] may produce a [[pain wind-up]] phenomenon. This triggers changes that lower the threshold for pain signals to be transmitted. In addition, it may cause non-nociceptive nerve fibers to respond to, generate, and transmit pain signals.<ref name="Hansson-1998">{{cite book |title=Nociceptive and neurogenic pain |vauthors=Hansson P |publisher=Pharmacia & Upjon AB |year=1998 |pages=52–63}}</ref><ref name="Jena-2015">{{Cite journal|last1=Jena|first1=Monalisa|last2=Mishra|first2=Swati Mishra|last3=Pradhan|first3=Sarita|last4=Jena|first4=Swetalina|last5=Mishra|first5=Sudhansu Sekhar|date=2015-09-01|title=Chronic pain, its management and psychological issues: A review|url=https://innovareacademics.in/journals/index.php/ajpcr/article/view/7403|journal=Asian Journal of Pharmaceutical and Clinical Research|language=en|pages=42–47|issn=2455-3891|archive-date=2021-08-02|access-date=2024-01-24|archive-url=https://web.archive.org/web/20210802223143/https://innovareacademics.in/journals/index.php/ajpcr/article/view/7403|url-status=live}}</ref> Researchers believe that the nerve fibers that cause this type of pain are [[group C nerve fiber]]s; these fibers are not [[myelinated]] (have low transmission speed) and cause long-term pain.<ref name="Jena-2015"/><ref name="Dickenson-2002">{{Cite journal|last1=Dickenson|first1=Anthony H.|last2=Matthews|first2=Elizabeth A.|last3=Suzuki|first3=Rie|date=2002|title=Neurobiology of neuropathic pain: mode of action of anticonvulsants|url=https://onlinelibrary.wiley.com/doi/abs/10.1053/eujp.2001.0323|journal=European Journal of Pain|language=en|volume=6|issue=SA|pages=51–60|doi=10.1053/eujp.2001.0323|pmid=11888242|s2cid=31591435|issn=1532-2149|archive-date=2021-10-18|access-date=2024-01-24|archive-url=https://web.archive.org/web/20211018135400/https://onlinelibrary.wiley.com/doi/abs/10.1053/eujp.2001.0323|url-status=live}}</ref>

These changes in neural structure can be explained by [[neuroplasticity]].<ref name="Dickenson-2002" /> When there is chronic pain, the [[somatotopic arrangement]] of the body (the distribution view of nerve cells) is abnormally changed due to continuous stimulation and can cause [[allodynia]] or [[hyperalgesia]].{{Efn|The continuous sending of messages from one body part causes its somatotopic area to become larger than the normal state, and the brain of the area attaches more and abnormal energy and importance to the tissue stimuli of that part of the body.<ref name="Jensen, M.P. 20092">{{cite journal|vauthors=Jensen MP, Sherlin LH, Hakiman S, Fregni F|year=2009|title=Neuromodulatory approaches for chronic pain management: research findings and clinical implications|journal=Journal of Neurotherapy|volume=13|issue=4|pages=196–213|doi=10.1080/10874200903334371|doi-access=free}}</ref>}} In chronic pain, this process is difficult to reverse or stop once established.<ref name="Vadivelu N, Sinatra R.">{{cite journal |vauthors=Vadivelu N, Sinatra R |date=October 2005 |title=Recent advances in elucidating pain mechanisms |journal=Current Opinion in Anesthesiology |volume=18 |issue=5 |pages=540–7 |doi=10.1097/01.aco.0000183109.27297.75 |pmid=16534290 |s2cid=22012269}}</ref> [[EEG]] of people with chronic pain showed that brain activity and [[synaptic plasticity]] change as a result of pain, and specifically, the relative activity of [[beta wave]] increases and [[Alpha wave|alpha]] and [[theta wave]]s decrease.<ref name="Jensen, M.P. 20092"/>

Inefficient management of [[dopamine]] secretion in the brain can act as a common mechanism between chronic pain, [[insomnia]] and [[major depressive disorder]] and cause its unpleasant side effects.<ref>{{Cite journal|last1=Finan|first1=Patrick H.|last2=Smith|first2=Michael T.|date=June 2013|title=The comorbidity of insomnia, chronic pain, and depression: dopamine as a putative mechanism|journal=Sleep Medicine Reviews|volume=17|issue=3|pages=173–183|doi=10.1016/j.smrv.2012.03.003|issn=1532-2955|pmc=3519938|pmid=22748562}}</ref> [[Astrocytes]], [[microglia]] and [[satellite glial cell]]s also lose their effective function in chronic pain. Increasing the activity of microglia, changing microglia networks, and increasing the production of [[chemokine]]s and [[cytokine]]s by microglia may exacerbate chronic pain.<ref name="Panahi-2018" /><ref name="Ji-2013">{{Cite journal|last1=Ji|first1=Ru-Rong|last2=Berta|first2=Temugin|last3=Nedergaard|first3=Maiken|date=December 2013|title=Glia and pain: is chronic pain a gliopathy?|journal=Pain|volume=154|issue=Suppl 1 |pages=S10–S28|doi=10.1016/j.pain.2013.06.022|issn=1872-6623|pmc=3858488|pmid=23792284}}</ref> It has also been observed that astrocytes lose their ability to regulate the [[Electron mobility|excitability of neurons]] and increase the spontaneous activity of neurons in pain circuits.<ref name="Ji-2013" />