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=== Wind-up and temporal summation === To assess pain facilitation, researchers can test temporal summation of second pain. This refers to the process where neurons of the CNS react to repeated stimuli with an increased response. If one quickly repeats a fixed noxious stimulus 10 times, the last one will be experienced as more painful than the first. Researchers can measure the amount of βwind-upβ of the neurons by looking at the difference between the first and the last stimulus. In chronic pain conditions like [[fibromyalgia]], that difference is greater than in normal controls, suggesting these patients experience a heightened form of temporal summation (TS). Collin et al. tested this procedure in 48 ME/CFS patients, but the results were ambiguous. There was only a difference in wind-up compared to control subjects if the pain stimuli were administered to the finger and not to the shoulder.<ref name=":7">{{Cite journal | last = Collin | first = Simon M. | last2 = Nijs | first2 = Jo | last3 = Meeus | first3 = Mira | last4 = Polli | first4 = Andrea | last5 = Willekens | first5 = Barbara | last6 = Ickmans | first6 = Kelly | date = May 2017 | title = Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study | url = https://www.ncbi.nlm.nih.gov/pubmed/28535557 | journal = Pain Physician | volume = 20 | issue = 4| pages = E489βE497|issn=2150-1149|pmid=28535557|quote= | authorlink = Simon Collin | author-link2 = Jo Nijs | author-link3 = Mira Meeus | author-link4 = Andrea Polli | author-link5 = Barbara Willekens|via= | author-link6 = Kelly Ickmans}}</ref> Testing of temporal summation was part of the procedure in three other studies without it being the primary outcome measure. One study<ref name=":12">{{Cite journal | last = Hermans | first = Linda | last2 = Nijs | first2 = Jo | last3 = Calders | first3 = Patrick | last4 = De Clerck | first4 = Luc | last5 = Moorkens | first5 = Greta | last6 = Hans | first6 = Guy | last7 = Grosemans | first7 = Sofie | last8 = Roman De Mettelinge | first8 = Tine | last9 = Tuynman | first9 = Joanna | date = Nov 15, 2017 | title = Influence of Morphine and Naloxone on Pain Modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia, and Controls: A Double-Blind, Randomized, Placebo-Controlled, Cross-Over Study | url = http://dx.doi.org/10.1111/papr.12613 | journal = Pain Practice | volume = 18 | issue = 4 | pages = 418β430|doi=10.1111/papr.12613|issn=1530-7085|quote= | authorlink = Linda Hermans | author-link2 = Jo Nijs | author-link3 = Patrick Calders | author-link4 = Luc De Clerck | author-link5 = Greta Moorkens|via=}}</ref> found TS to be higher in ME/CFS patients than controls, while two others did not find significant differences.<ref name=":13">{{Cite journal | last = Meeus | first = Mira | last2 = Ickmans | first2 = Kelly | last3 = Struyf | first3 = Filip | last4 = Hermans | first4 = Linda | last5 = Van Noesel | first5 = Kevin | last6 = Oderkerk | first6 = Jorinde | last7 = Declerck | first7 = Luc S. | last8 = Moorkens | first8 = Greta | last9 = Hans | first9 = Guy | date = Mar 2013 | title = Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? A double-blind randomized controlled cross-over trial | url = https://www.ncbi.nlm.nih.gov/pubmed/23511692 | journal = Pain Physician | volume = 16 | issue = 2| pages = E61β70|issn=2150-1149|pmid=23511692|quote= | authorlink = Mira Meeus | author-link2 = Kelly Ickmans | author-link3 = Filip Struyf | author-link4 = Linda Hermans | author-link5 = Kevin Van Noesel|via= | author-link6 = Jorinde Oderkerk | author-link8 = Luc Declerck | author-link8 = Greta Moorkens | author-link9 = Guy Hans}}</ref><ref name=":15" />
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