Indifference or hypersensitivity? Solving the riddle of the pain profile in individuals with autism

Abstract

Excitatory-inhibitory (E/I) imbalance is a mechanism that underlies autism spectrum disorder, but it is not systematically tested for pain processing. We hypothesized that the pain modulation profile (PMP) in autistic individuals is characterized by less efficient inhibitory processes together with a facilitative state, indicative of a pronociceptive PMP. Fifty-two adults diagnosed with autism and 52 healthy subjects, age matched and sex matched, underwent quantitative sensory testing to assess the function of the (1) pain facilitatory responses to phasic, repetitive, and tonic heat pain stimuli and (2) pain inhibitory processes of habituation and conditioned pain modulation. Anxiety, pain catastrophizing, sensory, and pain sensitivity were self-reported. The autistic group reported significantly higher pain ratings of suprathreshold single (P 5 0.001), repetitive (46˚C-P 5 0.018; 49˚C-P 5 0.003; 52˚C-P , 0.001), and tonic (P 5 0.013) heat stimuli that were cross correlated (r 5 0.48-0.83; P , 0.001) and associated with sensitivity to daily life pain situations (r 5 0.39-0.45; P , 0.005) but not with psychological distress levels. Hypersensitivity to experimental pain was attributed to greater autism severity and sensory hypersensitivity to daily stimuli. Subjects with autism efficiently inhibited phasic but not tonic heat stimuli during conditioned pain modulation. In conclusion, in line with the E/I imbalance mechanism, autism is associated with a pronociceptive PMP expressed by hypersensitivity to daily stimuli and experimental pain and less-efficient inhibition of tonic pain. The latter is an experimental pain model resembling clinical pain. These results challenge the widely held belief that individuals with autism are indifferent to pain and should raise caregivers' awareness of pain sensitivity in autism.

Interoception in Autism: A Narrative Review of Behavioral and Neurobiological Data

“… 44 In autism, pain processing differences have been found for pain processing, pain coping, and attenuation of pain. 76 , 83 , 85 Attenuation of pain, in particular, is an important element of the interoceptive-visceromotor loop, an aberrance on this loop could lead to downstream attentional, social and behavioral symptomatology. 42 , 88 Thus to summarize, there is evidence for pain processing differences in autism, and such differences may have cascading effects, though further work is needed.…”

Likely Pathogenic Variants of Cav1.3 and Nav1.1 Encoding Genes in Amyotrophic Lateral Sclerosis Could Elucidate the Dysregulated Pain Pathways

“…CACNA1D gene mutations are known to cause aldosteronism and neuromuscular abnormalities, not to mention neurological abnormalities in autism spectrum disorder and epilepsy, and in primary aldosteronism, seizures and neurological abnormalities (PASNA) [ 25 , 26 ], although no relation to ALS has been reported yet. Indeed, it is indicative of our theory that a recent study presented in autism—which also used to be considered a painless disorder [ 27 ]—exhibits sensory hypersensitivity to daily stimuli and to experimental pain [ 28 ]. Furthermore, we also aimed to reanalyze the pathomechanistic pathways downstream, including the genes of the Piezo2 channel as the site of the primary damage, as explained through the new non-contact dying-back injury mechanism theory of ALS [ 18 , 20 ].…”