There was some discussion in comments to another answer that I think are worth it to pose this as its own question.

Does insufficient (analgesic) treatment of acute pain increase the risk of its chronification (e.g. via continued pain signalling)?

For migraine for example, the following review presents insufficient acute pain relief as a mechanism for chronification twice in its Figure 1:

  • Insufficient acute pain relief leads to increased sensitization and thereby to chronification
  • Insufficient acute pain relief leads to increased intake of acute medication and thereby chronification

It further claims that

ineffective acute treatment of migraine is a major risk factor for chronification. This fact cannot be stressed enough, as it could be so easily avoided: recent data in over 5,000 patients with migraine in the American Migraine Prevalence and Prevention Study showed that ineffective acute treatment doubled the risk for migraine chronification compared with effective acute treatment [...] Moreover, longer exposure to headaches might promote sensitization processes and thereby promote headache chronification [...] Patients whose acute headache medication is insufficient experience longer and more severe pain than do patients with effective acute medication; this insufficient control of pain could lead to longer-lasting central sensitization and predisposes to migraine progression.

May, A., Schulte, L. Chronic migraine: risk factors, mechanisms and treatment. Nat Rev Neurol 12, 455–464 (2016). https://doi.org/10.1038/nrneurol.2016.93

It cites this observational study from 2015 which found that the effectiveness of acute pain treatment (i.e. triptanes, NSAID which was not conflated with preventative strategies) predicts chronification outcome.

Among 5,681 eligible study respondents with EM in 2006, 3.1% progressed to CM in 2007. Only 1.9% of the group with maximum [acute pain] treatment efficacy developed CM. Rates of new- onset CM increased in the moderate treatment efficacy (2.7%), poor treatment efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. In the fully adjusted model, the very poor treatment efficacy group had a more than 2-fold increased risk of new-onset CM (odds ratio 5 2.55, 95% confidence interval 1.42–4.61) compared to the maximum treatment efficacy group.

Conclusion: Inadequate acute treatment efficacy was associated with an increased risk of new-onset CM over the course of 1 year. Improving acute treatment outcomes might prevent new-onset CM, although reverse causality cannot be excluded.

Lipton RB, Fanning KM, Serrano D, Reed ML, Cady R, Buse DC. Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine. Neurology. 2015 Feb 17;84(7):688-95. doi: 10.1212/WNL.0000000000001256. Epub 2015 Jan 21. PMID: 25609757; PMCID: PMC4336107.

I am interested if there are other studies confirming this in migraine or other types of pain, and if there is an understanding of the pathophysiological mechanism behind it (one can imagine that continued pain signalling leads to long term potentiation of central pathways involved in pain sensation, but it would be nice to know whether this mechanism of action has been confirmed in experimental studies).

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    I'm kind of questioning the whole "chronification" idea. Maybe that's stupid of me, but everything can "chronify". If undertreatment chronifies, and over use of analgesics chronifies, and chronification occurs more in women (a big Woah there!) and chronification only doubles in a certain select population, and even people who are well and aggressively treated progress to "chronification", and a whole lot more if's, what does it even tell us about chronification, except that it's multifactorial with a chance of meatballs? Posted as a comment because it's a frame challenge. Mar 22 at 14:57
  • I think you should specify that we are talking about episodic or longer-term pain (like those coming with bigger surgery, structural problems, or neuropathic ones), since AFAIK central sensitisation is necessary and does not occur when the pain is below s certain threshold in frequency or duration as well as intensity. Mar 22 at 15:28
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    @PhilipKlöcking - You're the one who brought up migraines as an example of chronification! "@RayButterworth Regarding your migraine example...if you don't do anything about it (not even searching rest and a quiet surrounding), you will end up with chronic inflammation and chronic pain. Pain and inflammation (generally, immune response) are so closely linked that it is basically never a good idea to ignore any substantial and/or persistent pain." Mar 22 at 16:21


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