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Hypersensitivity Underlies the Pain Profile of Autistic People

The largest study investigating pain perception in autism dismisses the assumption that autistic people are indifferent to pain.

Lincoln Tracy

5 May 2023

PRF News

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The largest study investigating pain perception in autism dismisses the assumption that autistic people are indifferent to pain.

There is a common assumption that autistic people are hyposensitive to pain, potentially originating from the Diagnostic and Statistical Manual of Mental Disorders’ description of the sensory atypicality in autism as “an apparent indifference to pain/temperature.”

However, a significant portion of autistic people – over 80% in some studies – experience disturbances in sensory processing, which are often associated with a hypersensitivity to pain.

Consequently, whether autistic people are indifferent or hypersensitive to pain remains largely unknown.

Emerging evidence shows that autistic individuals display hypersensitivity to thermal pain, in addition to being unable to efficiently inhibit continuous pain. The research, conducted by Tseela Hoffman, a PhD student at the University of Haifa, Israel, shows that autistic people have a “normal” functioning peripheral nervous system, but report enhanced pain ratings when exposed to suprathreshold stimuli, as well as a reduced ability to inhibit tonic pain stimuli.

The new research is an important step forward in a challenging field, according to David Moore, Liverpool John Moores University, UK, a researcher experienced in assessing pain in vulnerable populations – such as autistic people – but not involved in the current study.

“This paper takes a systematic approach to understanding whether the sensory architecture is different in the autistic population, and if there are differences, where do they lie,” he told Pain Research Forum.

“A number of earlier papers in the field focused on static pain thresholds. While the current paper didn’t ignore those, it primarily explored more of the central systems, like temporal summation or conditioned pain modulation, in more depth than we have been able to before.”

The paper can be found in the April 2023 issue of PAIN.

A complicated etiology presents multiple potential explanations

Irit Weissman-Fogel (University of Haifa), Tami Bar-Shalita (Tel Aviv University), and Yelena Granovsky (Rambam Health Care Campus and Technion Medical School) – joint senior researchers from Israel – had previously explored pain sensitivity in people with sensory overresponsiveness, finding these individuals to have pain hypersensitivity and delayed pain inhibition processes.

“As there is a high incidence of sensory overresponsiveness in autistic people, we had assumed that pain hypersensitivity also characterizes autism,” they told PRF via email. Despite this assumption, there is scant literature and few laboratory studies investigating pain in autistic individuals.

In addition, autism etiology is multifactorial and not yet fully understood, although numerous mechanisms and theories have been proposed. One suggested mechanism is an excitatory-inhibitory imbalance of synaptic transmission at the single cell level, which could ultimately disrupt central nervous system activity (including the neural circuitry associated with pain responses).

The authors felt quantitative sensory testing would be the most appropriate way to adequately test both excitatory and inhibitory processes of pain perception, as well as verify the results across multiple experimental paradigms. Fortunately, Weissman-Fogel, Bar-Shalita, and Granovsky all had extensive experience in quantitative sensory testing, and they enthusiastically sought to put the excitatory-inhibitory imbalance theory to the test.

Assessing the imbalance theory

The authors recruited 104 adults (84 men; 52 autistic people, age- and sex-matched to a neurotypical control; median age of 25.5 years) – making this the largest sample size for a study exploring pain perception in autistic people to date.

Participants completed a suite of self-report questionnaires, including specific questionnaires exploring autism characteristics and sensory responsiveness, along with other questionnaires on areas known to interact with pain perception and responses (state-trait anxiety, pain catastrophizing, etc.).

After the questionnaires, participants underwent a thorough quantitative sensory testing protocol that assessed thermal detection (cool, warm) and heat pain thresholds, heat pain sensitivity, temporal summation, habituation, and both phasic and tonic conditioned pain modulation.

No specific hypotheses were tested, as the authors placed greater emphasis on examining the functioning of the excitatory and inhibitory pain pathways in autistic individuals. However, pain ratings and responses were compared between autistic individuals and the neurotypical controls.

Important similarities, but more important differences

While autistic individuals had similar heat and pain thresholds when compared to neurotypical individuals, several of the quantitative sensory testing paradigms revealed a persistent pattern of pain hypersensitivity among autistic individuals, especially when suprathreshold temperatures were involved.

For example, during the heat pain sensitivity testing (involving a series of 20 phasic stimuli at 46°C, 49°C, and 52°C with less than one second duration for each stimulus), autistic individuals reported significantly higher pain ratings (mean rating of 38.4 on a 0-100 numeric scale for the 52°C stimuli) than neurotypical controls (mean rating of 24.2).

Pain hypersensitivity was also observed in the temporal summation and habituation aspects of the quantitative sensory testing protocol. The authors attributed this hypersensitivity in autistic individuals to greater autism severity and sensory hypersensitivity to daily stimuli.

Both groups of participants displayed a similar efficiency in the phasic conditioned pain modulation component, although autistic individuals also displayed pain hypersensitivity here (by giving higher pain ratings for both the test and conditioning stimulus).

There were no differences in the pain ratings in response to the tonic pain stimulus within the conditioned pain modulation paradigm. However, autistic people displayed an inability to inhibit continuous pain: after 20 seconds of continuous heat stimulation, the authors did not observe the pain-inhibiting-pain phenomenon. This suggests autistic individuals have less efficient inhibitory pain processing.

From a neurobiological perspective, an imbalance between glutamate (an excitatory neurotransmitter) and GABA (an inhibitory neurotransmitter) activity may contribute to an excitatory-inhibitory imbalance in the brain. Although there is inconclusive evidence as to whether glutamate activity is disrupted in autistic individuals, there is consistent evidence of disrupted GABA activity.

As both GABA and glutamate play key roles in pain processing, the authors believe that decreased GABA activity contributes to the altered nociceptive profile in autistic individuals.

“The neuro- and biopathology in autism support our findings that the excitatory-inhibitory imbalance may interfere with the pain system, inducing facilitatory processes and altering the endogenous analgesia mechanisms,” the authors concluded in their manuscript.

The findings were of interest to Moore.

“Although autistic people may have similar pain thresholds to neurotypical individuals, once you go beyond that point you may hit distress in an autistic population far quicker. Autistic people seem to be rating the pain far higher than their non-autistic counterparts,” he told PRF.

However, Moore was quick to point out one of the challenges when researching pain sensitivity and responses in autistic individuals.

“The rating scales we use are calibrated within a neurotypical population. So, it’s possible [autistic people] are using this scale differently, or they’re rating something other than the exact thing we’re asking.”

Yet, the authors provide evidence that may refute this, by finding consistency within pain ratings to various psychophysical tests as well as with the self-report pain sensitivity questionnaire.

Moore also iterated how challenges such as these underline the importance of co-designing research with autistic people to maximize the likelihood of getting an answer to the question you have asked.

Opportunity for impact beyond the academic world

Weissman-Fogel, Bar-Shalita, and Granovsky are eager to build on these new findings, with plans to investigate the neurophysiological and autonomic correlates of pain, as well as identifying potential subgroups of autistic individuals based on their individual responses to pain.

Moore concurred with the author’s plans to explore individual differences in more detail.

“Looking at how particular [pain] profiles within autistic populations may alter the pain response is going to be a critical next step, particularly once we move away from such a controlled laboratory environment,” he told PRF.

The challenges associated with this kind of research are not lost on Weissman-Fogel, Bar-Shalita, and Granovsky, however, they are confident their work will make important contributions beyond academia.

“Our findings may raise physician, parent, and caregiver awareness of pain sensitivity in autism, which could lead to early and effective treatment [of pain], and ultimately improve the wellbeing and quality of life for autistic individuals and their families,” they told PRF.

Lincoln Tracy is a researcher and freelance writer from Melbourne, Australia. You can follow him on Twitter @lincolntracy.



Indifference or hypersensitivity? Solving the riddle of the pain profile in individuals with autism. Hoffman T, Bar-Shalita T, Granovsky Y, Gal E, Kalingel-Levi M, Dori Y, Buxbaum C, Yarovinsky N, Weissman-Fogel I. PAIN. 164(4): p791-803. April 2023.

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