Offset analgesia identifies impaired endogenous pain modulation in pediatric chronic pain disorders

Abstract

Offset analgesia (OA), a psychophysical test of endogenous pain inhibition, is diminished in many adult chronic pain disorders but OA has not been investigated in youth with chronic pain disorders. This study assessed OA responses in 30 youth with chronic primary and secondary pain disorders and 32 healthy controls. The OA, control, and constant thermal tests were evoked with an individualized noxious heat stimulus of approximately 50/100 mm on a visual analogue scale followed by 1°C offset temperature. This study also examined the association of OA responses with 2 self-report measures of pain sensitivity, the Central Sensitization Inventory (CSI) and Pain Sensitivity Questionnaire. Patients exhibited diminished capacity to activate OA with a reduction in ΔeVASc of 53 ± 29% vs controls 74 ± 24% (P = 0.003) even after multivariate regression adjusting for age, sex, and body mass index. Patients also showed decreased ability to habituate to a constant noxious heat stimulus compared to controls (P = 0.021). Central Sensitization Inventory scores showed excellent predictive accuracy in differentiating patients from controls (area under the curve = 0.95; 95% CI: 0.91-0.99) and CSI score ≥30 was identified as an optimal cutoff value. Pain Sensitivity Questionnaire scores did not differentiate patients from controls nor correlate with OA. In this study, 60% of youth with chronic pain showed reduced capacity for endogenous pain inhibition.

Unique features of central neuropathic pain in multiple sclerosis: Results of a cluster analysis

“…These features can be associated with each other, but causative relations cannot be deduced from the present study. PA and OA reflect the function of endogenous pain inhibition mechanisms (D’Agata et al, 2015; Shulman et al, 2020; Zhang et al, 2018), the alterations of which – owing to MS‐lesions – may contribute to enhanced activity and reactivity of spinal nociceptive neurons, hence to centrally mediated hyperalgesia (Campbell & Meyer, 2006). Hyperalgesia can also result from sensitized nociceptors (Treed et al, 1992; Woolf, 2011), which in MS may occur due to secondary consequences of the disease, including poor posture and/or balance, muscle weakness and muscle spasm (Brola et al, 2014; Truini et al, 2013).…”

“…Sensory testing then commenced following a training session. Testing included: (1) the measurement of warm sensation threshold and cold sensation threshold, as indicators of spinothalamic conduction (Willis & Westlund, 1997); (2) mechanical detection threshold, as an indicator of the dorsal column/medial lemniscal conduction (Noback et al, 2012); (3) the thermal grill illusion, as an indicator of central integration of thermal pathways and pain (Craig & Bushnell, 1994; Jutzeler et al, 2017); and (4) pain adaptation and offset analgesia, as indicators of central pain inhibition (D’Agata et al, 2015; Shulman et al, 2020). Testing was done in a random order.…”

<p>Commentary: Novel Use of Offset Analgesia to Assess Adolescents and Adults with Treatment Resistant Endometriosis-Associated Pain</p>

“…Notably, this standard 3-temperature paradigm has not been tested in a MRI setting with a pediatric population; however, OA was assessed in youth with chronic pain one time (outside MRI), applying an individualized noxious thermal stimulus of 50/100 on a VAS. 37 Using a thermal stimulator which is placed in contact with the skin, a preset computer-controlled temperature paradigm delivers the specific temperature pattern with the subject rating their pain in real time. A response to this dynamic test stimulus or offset trial ( Figure 1A ) consists of a reduction in self-reported pain intensity when the test temperature is applied for 5 seconds, raised by 1°C for 5 seconds, reduced by 1°C, and held for 20 seconds.…”

“…Recent studies report decreased or absent OA responses in patients with fibromyalgia, 38 neuropathic pain, 17 migraine, 39 and chronic pain of various etiologies. 36 , 37 , 40 In addition, three studies focusing only on chronic patients indicated decreased OA responses in patients with diabetic polyneuropathy, knee osteoarthritis, 19 and chronic radicular pain 17 , 18 , 20 although there was large interindividual variation. In patients with chronic pain, the attenuation of OA effects was observed by delayed offset and a relatively minor decrease in pain scores following the 1°C decrease in temperature as opposed to the disproportionately large reduction in pain perception among healthy controls ( Figure 1 ).…”

Development and Feasibility of the Headache-Related Light and Sound Sensitivity Inventories in Youth

“…One proposed mechanism for the presence of these atypical sensory sensitivities in adult headache patients is central sensitization of the nervous system [7,8]. Importantly, recent evidence does support the presence of central sensitization in youth with chronic headaches [9,10].…”