Self-injury Linked to Altered Pain Processing in Autism

Pam Harrison

May 18, 2016

BALTIMORE ― Adolescents with autism spectrum disorder (ASD) are more likely to engage in self-injurious behavior if they also have intellectual and developmental disabilities. In addition, self-injurious behaviors are more severe and persistent in lower-functioning patients with ASD, new research indicates.

"Children with autism are at significant risk for the development of self-injurious behavior, and the reigning model of self-injury posits that individuals with autism are injuring themselves because of pain insensitivity," James Bodfish, PhD, professor of hearing and speech sciences and neuroscience, Vanderbilt University Medical Center, Nashville, Tennessee, told a press briefing at the International Meeting for Autism Research (IMFAR) 2016.

"But our work suggests that at least a subgroup of individuals with chronic, repetitive, self-injurious behavior may be in a physiological state similar to neuropathic pain or hyperalgesia and that this state is associated with alterations in inflammatory, immune, and nociceptive systems."

New Treatment Targets?

In two studies carried out in collaboration with Frank Symons, PhD, University of Minneapolis, in Minnesota, the investigators recruited 81 adolescents with ASD. The patients were divided into those with intellectual and development impairments and those who had no intellectual impairment, as reflected by IQ scores of either less than 70 or greater than 90.

Ten patients were excluded from the study, leaving 30 patients with ASD and cognitive impairment (ASD + ID) and 41 patients with ASD only (ASD-only). Both groups were assessed for the presence and severity of self-injurious behaviors using a multimethod phenotypic battery of tests.

Self-injurious behaviors occurred in 63% of the ASD + ID patients compared with 24% of the ASD-only group. The severity of the behaviors was significantly more pronounced in the group with intellectual and developmental impairment (P = .002), Dr Bodfish reported.

The 34 adolescents with severe self-injurious behavior — defined as behavior that occurred at least daily and that had persisted for at least 12 months — were then subjected to a series of interventions, as were 17 other patients with ASD who were matched for age and IQ but who did not engage in self-injurious behavior.

A skin sample was taken from each patient to quantify epidermal nerve findings. Saliva samples were taken to evaluate different biologic markers associated with pain and stress.

Investigators also carried out quantitative sensory testing, in which different sensory stimuli — heat, cold, deep pressure — were applied at a level of intensity that was just below the pain threshold. Facial reactions to the different stimuli were assessed.

"There were differences in all three areas between the self-injurious group and the non-self-injurious group," said Dr Bodfish. For example, the group who engaged in self-injurious behavior had about a twofold increase in nonverbal reaction to painful stimuli.

"We also saw marked differences in nerve morphology in terms of density and distribution between the two groups," Dr Bodfish added. There were also changes in immune cells accompanied by degranulation of mast cells in the skin, corresponding to a heightened inflammatory response in ASD patients who engaged in self-injurious behavior.

"Together, our behavioral and biologic methods suggest that there are alterations in pain signaling in ASD individuals with self-injurious behavior, and what these findings could provide is a new set of biologic targets that could be used to think about developing novel treatments," he concluded.

"Striking" Differences

In a related study presented by Michelle Failla, PhD, also from Vanderbilt University, researchers used fMRI to visualize neural responses to painful stimuli. Dr Failla explained that objective markers of pain, such as neural responses obtained in conjunction with neuroimaging, help clarify the pain experience in vulnerable populations, such as persons with ASD who cannot verbalize their pain.

The study included 16 adults with ASD and 16 adults without ASD. The ASD group was divided into those who engaged in self-injurious behaviors and those who did not.

"Neural response to sustained heat pain was assessed with fMRI, and for each trial, heat was applied to the right lateral calf for 21 seconds — 15 seconds at target temperature, 3 seconds ramp up/down — followed by a 39 second rest period," said Dr Failla.

During the first 10 seconds of the heat test, adults with ASD displayed brain responses that were similar to those of the comparison group of typical adults.

However, during the next 10 seconds, as well as after the painful stimuli had been removed, "there was a highly exaggerated suppression of the neural pain signature in ASD subjects compared with controls (P < .001)," Dr Failla reported. In previous work, the group identified a neural pain signature using fMRI that differentiates pain from innocuous stimulation.

The widespread, late suppression of the neural pain observed in ASD patients was also more visible in the subgroup of ASD patients who engaged in self-injurious behaviors, she added.

Dr Failla concluded that the contrast between pain ratings and thresholds that were equivalent between the two groups and the "striking differences" in the neural pain response seen among ASD patients, especially among those who self-harmed, suggests that for individuals with ASD, the experience of pain may be altered in a manner not reflected in their subjective pain ratings.

Heartbreaking Behavior

Geraldine Dawson, MD, president of the International Society for Autism Research and professor of psychiatry and behavioral science at Duke University School of Medicine, Durham, North Carolina, told Medscape Medical News that one of the most challenging and heartbreaking struggles in autism is when a children or adults with autism harm themselves.

"We have had very little understanding as to why someone would engage in self-injury," Dr Dawson added.

"And sometimes the self-injury is to the level where it is causing a tremendous amount damage, and it is often treatment resistant, so you can imagine for a parent whose child is engaging in self-injury just how distressing it is, particularly when we don't have effective treatments," she said.

By using innovative methods to measure whether a nonverbal ASD patient is experiencing pain — facial expressions in the study by Dr Bodfish and colleagues, and fMRI in the study by Dr Failla's group, "they found that, in fact, individuals with autism who engage in self-injury experience perhaps even higher levels of pain than those without ASD," Dr Dawson observed.

Knowing this would make a parent even more concerned about their child who is engaging in self-harming behavior, she acknowledged.

Dr Dawson suggested that having observed that patients with ASD who self-harm have enhanced levels of inflammation may give researchers an opportunity to explore the possibility that treatments to reduce inflammation might be harnessed in the treatment of self-injury in individuals with ASD, and even in those without.

Dr Bodfish, Dr Failla, and Dr Dawson report no relevant financial relationships.

International Meeting for Autism Research (IMFAR) 2016: Abstracts 140.004 and 140.003, presented May 13, 2016.


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