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Central sensitization
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== Treatment of central sensitization == Nijs & Meeus wrote two reviews<ref>{{Cite journal | last = Nijs | first = Jo | last2 = Meeus | first2 = Mira | last3 = Van Oosterwijck | first3 = Jessica | last4 = Roussel | first4 = Nathalie | last5 = De Kooning | first5 = Margot | last6 = Ickmans | first6 = Kelly | last7 = Matic | first7 = Milica | date = 2011-01-22 | title = Treatment of central sensitization in patients with ‘unexplained’ chronic pain: what options do we have? | url = http://dx.doi.org/10.1517/14656566.2011.547475 | journal = Expert Opinion on Pharmacotherapy | volume = 12 | issue = 7 | pages = 1087–1098|doi=10.1517/14656566.2011.547475|issn=1465-6566|quote= | authorlink = Jo Nijs | author-link2 = Mira Meeus | author-link3 = Jessica Van Oosterwijck | author-link4 = | author-link5 = Margot De Kooning|via=}}</ref><ref name="Nijs2014">{{Cite journal | last = Nijs | first = Jo | last2 = Malfliet | first2 = Anneleen | last3 = Ickmans | first3 = Kelly | last4 = Baert | first4 = Isabel | last5 = Meeus | first5 = Mira | date = 2014-06-15 | title = Treatment of central sensitization in patients with ‘unexplained’ chronic pain: an update | url =http://dx.doi.org/10.1517/14656566.2014.925446 | journal = Expert Opinion on Pharmacotherapy | volume = 15 | issue = 12 | pages = 1671–1683|doi=10.1517/14656566.2014.925446|issn=1465-6566|quote= | authorlink = Jo Nijs | author-link2 = | author-link3 = | author-link4 = Isabel Baert | author-link5 = Mira Meeus|via=}}</ref> on the treatment of central sensitization. While it is advised to eliminate peripheral nociceptive input as this might sustain CS, the focus lies on medications that target the CNS. One example is acetaminophen (paracetamol) that reinforces the inhibitory serotonergic pathway. Meeus & Nijs tested this in ME/CFS patients with comorbid fibromyalgia. Although pain thresholds rose, there was no influence on temporal summation or conditioned pain modulation.<ref name=":13" /> Selective serotonin reuptake inhibitors (SSRI, such as fluoxetine) also activate the serotonergic descending pathways. In a 2011 study, Meeus & Nijs gave their test subjects intravenous SSRI (citalopram) but the trial had to be stopped prematurely since the medication gave too many side-effects.<ref>{{Cite journal | last = Meeus | first = Mira | last2 = Ickmans | first2 = Kelly | last3 = De Clerck | first3 = Luc S. | last4 = Moorkens | first4 = Greta | last5 = Hans | first5 = Guy | last6 = Grosemans | first6 = Sofie | last7 = Nijs | first7 = Jo | date = Nov 2011 | title = Serotonergic descending inhibition in chronic pain: design, preliminary results and early cessation of a randomized controlled trial | url = https://www.ncbi.nlm.nih.gov/pubmed/22021700 | journal = In Vivo (Athens, Greece) | volume = 25 | issue = 6 | pages = 1019–1025|issn=1791-7549|pmid=22021700|quote= | authorlink = Mira Meeus|via= | author-link8 = Jo Nijs}}</ref> [[Opioids]] (morphine, codeine etc.) form another option, although these drugs are rather controversial because they can lead to addiction and cause selective pain sensitization. In 2017 Meeus & Nijs tested morphine and naloxone (an opioid antagonist) against a placebo, but the results were rather bleak:<blockquote>“neither morphine nor naloxone influenced deep tissue pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/[[Fibromyalgia|FM]] or [[Rheumatoid arthritis|RA]].”<ref name=":12" /></blockquote>There are other therapeutic options to treat central sensitization like N-methyl-D-aspartate –receptor antagonists (e.g. ketamine), GABA-antagonists (e.g. pregabalin) or a ketogenic diet. Nijs & Meeus also propose exercise therapy and emphasize that a time-contingent approach is to be preferred in treating CS: <blockquote>“A symptom-contingent approach may facilitate the brain in its production of nonspecific warning signs like pain, whereas a time-contingent approach may deactivate [[brain]]-orchestrated top-down pain facilitatory pathways.”<ref name="Nijs2014" /> </blockquote>The authors do however caution that this approach might not work in every CS-patient group: <blockquote>“some patients with CS pain, including those with chronic whiplash associated disorders , chronic fatigue syndrome and fibromyalgia, are unable to activate endogenous analgesia following exercise. It remains to be established whether long-term exercise therapy accounting for the dysfunctional endogenous analgesia is able to ‘treat’ CS in these patients.” </blockquote>
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