Table 1 Comparison between the formalin-induced inflammatory pain model and clinical observations of ASD patients

Increases of inflammatory cytokines such as TNF-α and IL-1β in the blood and the brain

Elevation of TNF-α in cerebrospinal fluid of autistic children [66].

Yes

Elevated levels of the pro-inflammatory cytokine, including IL-1, IL-6, IL-12, IL-23, TNF-α, and BDNF [67].

A trend toward a significantly increased production of IL-6 and TNF-α in whole blood [68].

Increased plasma concentrations of IL-1b, IL-1RA, IL-5, IL-8, IL-12(p70), IL-13, IL-17, and GRO-a [69].

Impaired neurogenesis

Neuropathological developmental changes in the brain reflect multiregional dysregulation of neurogenesis, neuronal migration, and maturation [70].

Yes

Dysregulation of neurexin-1

Two putative missense structural variants were identified in the neurexin 1β gene [71].

Possibly yes

Disruption of oxytocin system and therapeutic effect of oxytocin

Significantly lower plasma oxytocin levels [72].

Yes

A significant correction of repetitive behaviors following oxytocin infusion [73].

Self-grooming and repetitive jumping (repetitive behaviors)

Significantly higher frequency and longer duration of repetitive and stereotyped behaviors [74].

Yes

Ritualistic and stereotypical behavior [75].

Sleep problem

Insomnia associated with neurochemical (abnormalities in serotonergic transmission or melatonin levels), psychiatric (anxiety), and behavioral (poor sleep habits) etiological factors [76, 77].

Yes

Treatments for insomnia show promise for behavioral/educational interventions [78].

Reduction of FMRP

Significantly reduced levels of FMRP protein [79].

Yes

Social memory deficits

Impaired on immediate and delayed recall of faces and of family scenes and impaired spatial working memory. Defective integrity of verbal working memory and impaired spatial working memory [80].

Yes

Axonal impairments

Area-specific changes below anterior cingulate cortex (ACC) included a decrease in the largest axons that communicate over long distances. Overexpression of the growth-associated protein 43 kDa accompanied by excessive number of thin axons that link neighboring areas. In the orbitofrontal cortex (OFC), axons had decreased myelin thickness [24].

Yes or partially yes

Decreased levels of proteins associated with myelination and increased synaptic and energy-related proteins in the prefrontal cortex. Opposite directional changes were found for myelination and synaptic proteins in the cerebellum [81].

Deficits in social activities

Developmental delays in social interaction, language, and imaginative function [82]

Yes or partially yes

Altered oxytocin system in CA2 region

Oxytocin is a key factor in CA2 regional social memory function [26, 83]. No direct human data available.

Potentially yes

ASD phenotypes are more prominent in male than in female animals.

Sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and ASD (greater male prevalence) [84, 85].

Yes,

Abnormal cell death

The abnormal apoptosis found in autism from postmortem [86].

Yes