The results of the study concluded that SMD, particularly neural under-responsiveness, can act as a potential risk element for CRPS and therefore screening for SMD is recommended. The study also allocates the risk index probability clinical tool to identify those at risk for CRPS immediately after the injury, but the consent for further research is needed.  

Complex regional pain syndromes are prominent in about 4-7% of patients after limb fractures, surgery or injuries. It is characterized by voluntary pain regionally related, disproportionate in its time duration and/or pain intensity after trauma or other lesions. The pain has a distal predominance of abnormal motor, sensory, sudomotor, vasomotor edema, and/or trophic characteristics. The evolution of CRPS varies that usually leads to a severe state of disablement in the affected limb, adversely affecting the quality of life. CRPS impose a vast individual and cost burden on society, typically reducing working hours and elevating overall costs. It has a prevalence rate of about 26.2 per 100,000 individuals in Europe and approximately 200,000 individuals are diagnosed with CRPS every year in America.

CRPS is categorised into two types: CRPS Type 1; identified by a noxious event or a cause of immobilisation with no recognised nerve injury that and CRPS Type 2; that involves distinct nerve injury (Type 2). The reason of CRPS is still unclear and various underlying pathophysiological mechanisms such as genetic and psychological factors; alterations in somatosensory innervation and sympathetic nervous system processing; peripheral and central sensitisation; aggravated local and systemic inflammatory cytokines levels; lower systemic levels of anti-inflammatory cytokines and catecholamines; and regulating neuroplasticity difficulties have been indicated. The best way to achieve clinical and optimum outcomes is an early diagnosis of CRPS and prompt rehabilitation. However, negligence to examine complicating factors retards the determination, and inappropriate treatment can lead to CRPS with severe disability. 

Various risk factors for the onset of CRPS have been indicated. It is prominent in females, mostly in postmenopausal women; individuals who had undergone an ankle injury such as dislocation or an intraarticular fracture, and a wrist fracture; individuals who are immobilised; and when the pain level is escalated, higher than usual, in early stages of post-trauma. Also, a significant association has also been reported between CRPS and a prior diagnosis of migraine or osteoporosis, but these potential risk factors were not confirmed across trials. The evidence has also not been identified for robust genetic associations, and psychological factors such as anxiety, depression, neuroticism have also not been shown to be predictors for CRPS development. Recently a higher incidence of posttraumatic stress disorder (PTSD) in CRPS, compared to the general population and other limb pain disorders was inferred suggesting that PTSD may also serve as a risk factor for developing CRPS.  The elements for CRPS onset are still evasive, recognising those at risk for CRPS before surgical interventions, immediate post-trauma, or very early in the condition, is warranted. 

A substantial body of literature about CRPS suggests the association of the central nervous system regarding sensory as well as pain processing changes. Especially, impairments in endogenous pain inhibitory pathways evident and SMD is associated with pain severity, showing pain hyperalgesia.   Moreover, sensory changes occurring in the contralateral hand were found associated with the ones happening in the affected hand, indicating central sensory processing alterations as well but till date, it is not clear whether these alterations are a result of or a predisposition for developing CRPS.  

Sensory modulation dysfunction (SMD), is a category of sensory processing disorder, that affects single or multiple neural systems and the capacity to regulate responses to sensory input in an adaptive manner. It also interferes with work performance, quality of life and participation in everyday routines. The incidence of the SMD was estimated to be 5–16% of the population, otherwise healthy. It is characterised by sensory over-responsiveness (demonstrated as a non-painful stimulus perceived as unpleasant, aversive, or painful) and sensory under-responsiveness (shown by a reduced response to stimulus). Sensory over responsiveness was found to be related to daily pain sensitivity. Sensory over responsiveness in children and adults has revealed hyperalgesia and prolonged duration of pain  lingering sensations, compared to controls, indicating modulation in endogenous pain in individuals with sensory over-responsiveness who are otherwise healthy 

Rationale behind research:

Identification of risk factors for CRPS onset is difficult, and to date, no specific clinical symptom has been empirically found to be a potential risk factor for the emergence of CRPS. Therefore this cross-study has been conducted to determine the potential risk factors in the incidence of  CRPS.

Objective:

The objective of the cross-sectional study was to determine the correlation between CRPS and SMD, specifically to elucidate whether SMD could be considered as a risk factor for CRPS.  

Study outcomes:

• Patient demographic characteristics were studied at baseline
• Other results analysed were risk factors for CRPS {age, gender, SRQ scores, CRPS signs and symptoms (CCS), SMD subtypes} and distribution of SMD and its subtypes  

Time Points: 3 months to 12 years

Outcomes

Baseline: There were no significant differences observed at baseline

Study outcomes:

• There were statistically significant differences found in the distribution of SMD and its subtypes (sensory over-responsiveness and sensory under-responsiveness ) in both CRPS and control group
• No statistically significant differences were found between SMD subtypes (Kruskal-Wallis test p>0.05) in each of the CRPS Severity Score parameters tested
• The risk of CRPS was found to be 8.21 and 2.68 times higher in individuals with sensory under- and sensory over-responsiveness, respectively, compared to non-SMD individuals (p = 0.01 and p = 0.03, respectively)

The findings of the study suggested that SMD can be a potential risk factor in explaining the presence of CRPS. Sensory under-responsiveness has a major likelihood in the occurrence of CRPS than sensory over-responsive or older in age. However, there were no statistically significant differences achieved in the CRPS severity between SMD subtypes within patients with CRPS. 

Examination of pain perception in daily life contexts suggests that SMD in healthy individuals co-occurs with regular pain sensitivity. Individuals with SMD have also explained pain perception alterations in response to laboratory quantitative sensory testing of pain stimuli. These alterations include hyperalgesia and pain after-sensation in comparison to healthy controls, suggestive of compromised endogenous pain modulation [41]. The persistent activation of facilitation increases sensitisation in the dorsal horn and leads to a state of chronic pain. The co-occurrence of pain sensitivity (i.e. CRPS) and SMD can be explained by their distinct pain processing regions in the brain, referred to as the pain matrix. The interconnected system of brain areas in the pain matrix indicated a significant BOLD fMRI response to stimuli, either nociceptive or other. Specifically, non-nociceptive and nociceptive somatosensory stimuli generate indifferent responses in S1 as well as in some portion of S2, suggesting that non-nociceptive or nociceptive stimuli are responsible for evoking part of neural activities determining the BOLD response. These fMRI findings, therefore, infer that the network of regions, (i.e. the pain matrix) are involved in nociceptive and non-nociceptive processing.  

Age was also accounted as a risk factor, but it was not a potential factor for the onset of CRPS. Females were thought to have a higher risk of developing CRPS. However, results were controversial, and there was a higher incidence of CRPS in postmenopausal women.  A study conducted in males determined that young men are more susceptible to develop CRPS. The present study results were also consistent with previous studies.