The impact of sex differences on perceived pain intensity in pain protocol standardization, 2024, Wragan et al

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Eleanor

Senior Member (Voting Rights)
Preprint
Abstract
Background: Sex differences have been widely demonstrated in both acute and chronic pain. Sex differences may have wider impact on research design and analysis than already established. This study addresses an important methodological aspect with regards to how sex differences could influence the design of standardized experimental pain protocols used to characterize an individuals pain response.

Methods: This study addresses sex differences of perceived pain at tonic heat pain threshold (HPT). Participants used a computerized visual analogue scale (CoVAS) to continually rated subjective pain intensity during tonic HPT. Metrics (Mean, Standard Deviation, Maximum) were extracted from the CoVAS to characterize perceived pain.

Results: Female participants rated pain intensity at HPT significantly lower than male participants across all extracted metrics used to characterize the coVAS rating. The effect of sex on the mean and standard deviation of pain intensity ratings at HPT was medium, while the effect size of sex on the maximum pain intensity rating at HPT was large.

Conclusion: The significant sex differences in perceived pain intensity at HPT indicates that methods of standardization to a specific pain intensity merit sex-specific consideration. Additionally, these observed sex differences underscore the necessity for sex specific design across both pre-clinical and clinical studies of pain.


https://www.biorxiv.org/content/10.1101/2024.12.09.626634v1?med=mas
 
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16 females and 23 males were used in the study. Participants had a mean age of 22.45 years old.
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Small sample size and any study of this type is going to be confounded by culture e.g. 'it's manly to ignore pain'.


CoVAS is an industry gold standard tool that allows participants to continually quantify their pain levels by displacing the marker of a 10 cm slider between the two endpoints of ‘no pain’ and ‘most intense pain imaginable’.
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This study is not what I thought it was. They first establish a heat pain threshold (HPT) for each participant. Then:
During ramp and hold trials, participants’ stimulating thermode was increased from baseline temperature to individuals’ HPT at a rate of 1.5°C/s. Once HPT was reached, this temperature was held for 30s before the thermode was returned to baseline temperature at a rate of 6°C/s. Throughout this entire procedure, participants’ subjective sensation of pain was captured in real-time using the CoVAS.
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VAS is visual analogue scale

Table 1 gives results for how the participants rated the pain at their identified heat pain threshold. The whole study is about the VAS, the rating of the pain. But they don't seem to tell us what the HPTs actually were i.e. what were the temperatures where participants reported pain and how did they vary by sex.
 
Yeah, there is nothing about the temperatures of the heat pain thresholds!

For what it is worth, the females did indeed rate the pain at their individualised HPT as lower.

Previous research has demonstrated females have lower temperature heat pain thresholds, as females are more sensitive and responsive to nociceptive stimulus[1, 2, 29] . Previous research also evidenced that women frequently report higher subjective pain intensity ratings relative to men across many diagnostic and experimental contexts[28]. However, this study reveals that even when participants are standardized to their individual threshold temperature, the temperature at which they first start to experience pain, women regard this threshold sensation ofpain as less painful. This identified sex difference in pain perception at threshold introduce complexity into attempts at individually standardizing research protocols, particularly those examining descending pain modulation. Individualizing these protocols to accommodate the heightened pain sensitivity of women may not resolve sex differences in subjective pain perceptions of threshold stimuli.
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It's quite possible that the women had, on average a lower Heat Pain Threshold because they were not culturally primed to feel that it was important to have a high pain threshold. As a result, they reported lower pain at the threshold, because the temperature was lower. (Although, who knows, perhaps the women had higher Heat Pain Thresholds in this study? The authors don't tell us.)

Surely a paper about pain perception that doesn't tell us about the level of painful stimulus applied (when they were different for each participant) is nonsense? What are the peer reviewers doing?
 
@Elaenor, why did you post this paper? Has it been cited somewhere?

A typically used metric is heat pain threshold (HPT), the lowest temperature at which an individual experiences pain. HPTs range from 42-49°C, and although sex differences are thought to be larger to mechanically induced pain relative to noxious heat[11], women typically report HPTs a single or few degrees lower than men [1, 12-14].
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Female mean perception of pain at their individual heat pain threshold = 23.7
Male mean perception of pain at their individual heat pain threshold =37.7
This is on a 0-100 scale, with 100 being worst pain imaginable.
 
Thanks for posting it. I think it's an interesting example of the mess the chronic pain literature is in. There's a bit of waffle in there about how chronic pain is a disease, when of course it's a symptom, one that can have a range of causes. Calling chronic pain a disease makes as much sense as calling fever a disease - understanding the underlying cause helps get the right treatment.

The paper reports that women tend to, on average, report a heat pain threshold that is one or two degrees lower than men. But, if women are on average reporting that the pain intensity at their heat pain threshold is only 24/100, while the men are reporting the pain intensity at their heat pain threshold is 38/100, then what can you conclude? Not much about sex differences in intrinsic pain thresholds I think. Possibly you can conclude something about how bad pain needs to be before men and women in the sampled population will report feeling pain in a pain study.
 
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I think this it relevant to men's and women's reporting of pain:https://www.theguardian.com/commentisfree/2024/oct/14/men-women-pain-school-period
Guardian article includes use of menstrual pain simulators to teach men about the level of pain many women endure monthly.

Quote:
To men who still want ‘proof’ of women’s pain: be careful what you wish for
This article is more than 1 month old
Rhiannon Lucy Cosslett

A UK school’s botched plan to require a doctor’s note for period pain shows we’re still not trusted over our own suffering.

How’s your pain threshold? For a few months now, I’ve been obsessively watching videos of men trying period pain simulators. The machines have wired abdominal pads that send electrical impulses controlled by a console that can replicate the ferocity of cramps on a range of one to 10. Often by five or six on the dial, men are groaning or even screaming in agony while their female partners, also hooked up to the machine, sit unfazed.

Like many, many women, I am habituated to a certain level of pain. From girlhood, we go about our lives in varying levels of agony, often with the people around us knowing little of our discomfort. There are days, though, when it all becomes too much. It used to be that all you had to do was vaguely mention “women’s problems” to be granted some respite. Not so any more, at least in some schools.

More at link
 
None of which makes any difference when it's common for physicians to assume they can tell, then go on to ignore the patient if there is any conflict between the two. Because this is entirely a matter of judgment about something that can't be independently verified. So even if there are some small differences between sexes, there are variations between individuals that make this irrelevant, and so many additional factors that go into increasing or lowering perception of pain. Even more so that all of this goes out the window when you involve the kind of pain you will see in health care settings, which have nothing at all to do with the levels that can be studied using lukewarm water and other artificial attempts.

Basically it's a lot like most of the fundamental issues humanity has faced from the beginning of civilization, things like fairness and justice, without technology nothing gets resolved, and some things can't be quantified technologically so cannot be resolved. Even more so that there are opinions out there that can directly conflict with individual cases, some people think suffering brings character, and other weird things.

There is a fundamental uncertainty principle going on when it comes to health that medicine knows but almost never fully applies. Usually they can't know for sure, and can't possibly verify, and that makes everything more complicated. Which isn't really the issue in itself, the problem is with the usual habit of making stuff up to account for this uncertainty, all of which come in and around the psychobehavioral ideology. It's a problem made worse by the addition of even more of the problem. All this junk nonsense about central sensitization and this weird obsession with making everything about illness be a behavioral issue and so on.

Basically, this is left to human judgment. Which is the worst thing to work with. So it's all terrible.
 
SNT Gatchaman said:
Rule #1: "Pain is what the patient says it is."
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I definitely understand the difficulties with this. That there are some people who do lie, but even then that means that there is a different problem, possibly more than one. But it's impossible to tell the difference, in the moment or with hindsight, so there is never any basis to reliably make such a judgment.

Also some of this exaggerating pain is likely to be an adaptation to the scarcity of health care, which leads to a lot of people falling down in priority, which can be remedied by exaggerating a bit, but all that means is you now have three problems and counting.

To think that all of this would just go away if we could just find one painkiller that works without causing problems, would not lead to habituation, or can be euphoric in some people in some circumstances, that somehow get applied to everyone. It would be completely transformative.

About as textbook an example of throwing babies out with the bathwater as it gets. Some people lie? Some people experience euphoria from opioids? Let's ruin the whole concept of pain management for everyone! Double time over with the completely failed war on drugs, where the drugs have won but everyone pretends like it's some stalemate.
 
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