Quantitative Sensory Testing for Pain: What Exactly Are We Measuring?

Introduction to QST

Quantitative Sensory Testing (QST) was developed by the German Research Association for Neuropathic Pain (DFNS) and can be broadly defined as a non-invasive protocol used to assess somatosensory function.^1,2 Specifically, QST aims to determine sensory loss (e.g. hypoesthesia, hypoalgesia) or sensory gain (e.g., hyperesthesia, hyperalgesia, allodynia) by assessing sensory function of large (Aβ-fibers) and small (Aδ- and C-fibers) sensory nerve fibers through the use of standardized stimuli.^1,3 QST is most often used to characterize underlying pain processes, namely peripheral and central sensitization. Peripheral sensitization is described as increased excitability in nociceptors in the peripheral nervous system which can lead to the development of hyperalgesia.⁴ Central sensitization is described as increased excitability of nociceptive neurons in the central nervous system which can lead to the development of allodynia and hyperalgesia.⁵

What is QST?

Research substantiates the use of QST for characterizing normal and pathophysiological pain perception, differentiating chronic pain conditions, generating pain modulation profiles (i.e., the inhibitory and facilitatory processes that regulate pain perception), and as a treatment outcome marker.⁶ QST consists of multiple stimulus modalities (e.g., thermal, mechanical, etc.) and both static and dynamic response measures that engage different nerve fibers, components of afferent somatosensory transmission, and central nervous system pain pathways.^7,8 Static measures include pain threshold, the point at which stimulus is first perceived as painful, and pain tolerance, the maximum pain level a person can tolerate from a stimulus. Commonly utilized dynamic response measures include temporal summation (TS) and conditioned pain modulation (CPM).⁹ TS occurs when a noxious stimulus, applied repeatedly at the same intensity, leads to an increase in perceived pain, suggesting sensitization. Conversely, decreased perceived pain would suggest habituation to the stimulus. TS is the psychophysical manifestation of wind-up; a pain facilitatory processing. CPM describes the inhibition of a noxious stimulus through the application of another noxious stimulus elsewhere on the body. CPM reflects the manifestation of diffuse noxious inhibitory controls – ascending projections from adverse stimuli trigger supraspinal regions which in turn activate descending inhibitory (opioidergic, serotonergic, noradrenergic) projections stemming from the spinal cord or brain regions.¹⁰ Individuals with chronic pain often exhibit abnormal pain processing compared to healthy controls, typically manifesting as decreased pain inhibition (shorter CPM duration) and increased pain facilitation (greater TS), which are associated with higher pain severity and greater disability in various chronic pain conditions and suggests central sensitization.^9,11–13 QST was strictly designed to measure responses to standardized stimuli, but may more accurately reflect psychological function rather than sensitization.

QST and the Biopsychosocial Model of Pain

Abnormal pain processing patterns, like sensitization, not only reflect physiological changes but are also influenced by certain aspects of psychological functioning and behavioral health. Pain, as most readers likely understand, is not only a sensory experience but also an emotional experience. Understanding the psychosocial correlates of dynamic QST measures is crucial, as factors such as emotional distress, cognitive appraisal, and maladaptive behaviors can significantly impact an individual’s pain experience. Notably, the biopsychosocial model of pain is a widely accepted framework used to understand chronic pain.¹⁴ This model posits that pain is not solely determined by biological/biomedical factors, as was historically believed.¹⁵ Instead, this heuristic and multimodal framework appreciates the critical role that non-biological factors play in the pain experience of humans. Research suggests that psychological factors (anxiety, depressive symptoms, pain catastrophizing, etc.) can modulate pain from a descending (top-down) pathway, whereby higher brain regions influence the processing of pain signals and either amplify or reduce pain perception.¹⁶ Studies using QST assessments have demonstrated associations between specific psychological factors and abnormal pain processing in controls (research participants without chronic pain) and patients with chronic pain.^3,17–21 In non-specific chronic low back pain (Ns-cLBP), which accounts for 90% of all cLBP cases, studies have demonstrated that altered pain sensitivity is associated with pain catastrophizing, anxiety and fear avoidance.^22–24 Similar findings were reported among patients with other idiopathic conditions (I.e., fibromyalgia and migraine headache).^25,26 Further, when seeking treatment, minoritized patients suffering from chronic pain (especially those with idiopathic conditions) often feel that healthcare providers do not recognize or validate their pain.¹⁵ This can lead to a self-perception that their pain is either inadequately expressed or illegitimate and may even invite blame from others, increasing the risk of both physical and mental health consequences.

The interplay between biological and psychological factors can intensify physical pain and exacerbate feelings of distress and injustice.^15,27 Implementing QST for these patients can provide valuable validation and insights into their pain experiences, and provide additional support to observed associations between stigma and clinical reports of pain.^28,29 Psychological factors and pain may also negatively impact behavioral functioning; sleep and exercise have been shown to impact pain sensitivity.^30–32 Even social isolation can negatively impact pain outcomes.³³ Chronic pain most often exists in the context of many overlapping conditions and QST has not been able to effectively parse these conditions. Even in the absence of chronic pain, individuals with significant mood symptoms can show altered pain processing.³⁴ Among those with chronic pain, dynamic measures of QST like CPM are often not consistently associated with clinical pain ratings and one recent study described it as best a proxy for resilience.^35,36 Due to the complex interaction between physiological and psychological factors in pain populations, it is challenging to confidently conclude that QST is only directly assessing pain-related sensitization rather than capturing a broader assessment of psychosocial functioning.

What is Sensitization?

QST is a complex and sophisticated methodology but is not without limitations that significantly constrain our ability to confidently state that it accurately assesses sensitization; most notably it cannot, by definition, assess sensitization directly. The International Association for the Study of Pain (IASP) defines sensitization as “increased responsiveness of nociceptive neurons to their normal input, and/or recruitment of a response to normally subthreshold inputs.”³⁷ Therefore, QST can only infer sensitization indirectly through hyperalgesia and allodynia because directly innervating and observing nociceptors is impractical in humans. Due to this discrepancy between QST outcomes and the actual nociception processing, psychosocial factors introduce bias. However, sensitization is currently facing conceptual challenges, prompting debates about what sensitization actually means. Definitions other than IASP’s have emerged over the years with varying conceptualizations.^38,39 Woolf suggests that pain hypersensitivity is the direct manifestation of central sensitization and attempts to elaborate further on IASP’s pure neural model to connect hypersensitivity to central processing of pain.⁴⁰ This seemingly does very little to deter the notion that psychosocial factors influence hypersensitivity. Others argue that sensitization is a global state that can be assessed using a questionnaire, such as the Central Sensitization Inventory (CSI).^41,42 However, it has recently been suggested that questionnaires like the CSI do not replicate our general understanding of sensitization but rather most closely assess pain-related hypervigilance, anxiety, and kinesiophobia.^43,44 Although, it could be argued that QST evoked pain responses are likely assessing psychological and behavioral functioning rather than central sensitization, similar to surveys like the CSI.^3,21,22

Sensitization has become a buzzword in spite of, or possibly thanks to, the lack of consensus within the community on what is being assessed. Van den Broeke et al. suggest a new “return to basics” definition conceptualizing sensitization as a stimulus response: “enhanced behavioral responsiveness that results from repeated or prolonged exposure to the same stimulus.”³⁹ This definition aligns with the original conceptualization of QST. Fillingim points out that this also reflects how we most often think about pain clinically; we learn about other’s pain through verbal or nonverbal communication, e.g. pain reports and pain behaviors.⁴⁵ However, this definition is not without limitations. For example, a clinician would not assume that a cLBP patient not displaying pain behaviors has suddenly been cured of their pain. Absence of evidence is not evidence of absence. Further, this still does not separate psychosocial functioning from pain experiences. Pain reports and behaviors are highly influenced by psychosocial factors.^46,47 Regardless of sensitization’s definition based in behavioral or biological conceptualizations, it does little to suggest that QST is a more accurate assessment of sensitization rather than general psychosocial functioning.

QST and Nociplastic Pain

Embracing QST’s utility as possibly a better assessment of psychosocial functioning may improve our understanding of pain. Interpreting QST outcomes as a biomarker for pain would be both inappropriate and shortsighted considering the growing literature suggesting its ability to assess more varied experiences. Pain is a highly dynamic experience, and the pain community is continuously working to develop and refine our understanding of pain. One example of this is the adoption of nociplastic pain, which was introduced by IASP in 2017 as a third pain descriptor alongside nociceptive and neuropathic pain.⁴⁸ Nociplastic pain is described by IASP as pain that arises from altered nociception despite no clear evidence of damage to tissue or the somatosensory system causing pain.³⁷ Although nociplastic pain may develop in any chronic pain condition, it is most notably associated with fibromyalgia, irritable bowel syndrome (IBS), temporomandibular disorder (TMD), and cLBP in which these conditions have documented changes in their nociceptive processing.^48–50 Previously these conditions were referred to as centralized pain conditions or simply as idiopathic pain conditions, meaning pain with an unknown origin.^49–51 Adopting this new classification reflects the understanding that chronic pain can exist as a primary disease and moves away from less specific terms like idiopathic and more stigmatizing terms like (dys)functional or pathological.^48,52

Perhaps QST is most useful when researching or clinically examining nociplastic pain where a combination of altered pain processing and presence of non-pain symptoms are involved. Guidelines proposed by IASP suggest that nociplastic pain is “probable” when pain lasts at least 3 months, hypersensitivity is present, symptoms are not explained by nociceptive or neuropathic pain, and non-pain comorbidities are present.⁵⁰ Non-pain symptoms include sleep disturbances, fatigue, cognitive deficits, mood disturbances, and general sensitivity to lights, sounds, and/or odors.^50,51 Many of these symptoms have been implicated in QST. Some researchers caution against using QST as a diagnostic tool citing large within- and between-individual heterogeneity in QST outcomes, observations of normal pain processing among nociplastic pain patients, and limited availability of QST.^50,51 Past researchers have argued that QST was most useful in exploring neuropathic pain but similar shortcomings limited QST’s utility including limited availability of standardized population norms and inability to connect to specific mechanisms.⁵³ Perhaps QST cannot provide the mechanism-based understanding of pain like the community hoped, but maybe broadening our understanding of QST can lead to more nuanced pain research.

Conclusion

QST pain responses may better reflect psychosocial functioning than underlying sensitization, providing a valuable opportunity to expand our understanding of pain experiences. Pain is a dynamic sensory and emotional experience that most likely has both behavioral and nonbehavioral aspects. This complexity presents a unique challenge in quantifying pain and its underlying processes. Research using QST has shown that psychosocial factors and pain are so closely intertwined that it is difficult to separate them. Growing research suggests that psychosocial factors may be more indicative of pain outcomes than vice versa. Therefore it may be more beneficial to target psychosocial factors to improve quality of life rather than pain directly.^46,54 Perhaps instead of striving to develop QST into an objective pain biomarker, future research should engage with its ability to assess psychosocial functioning in pain. Any inferences regarding pain processing through QST outcomes are filtered through an individualized experience. Some researchers refer to QST as semiobjective because of this influence.⁵⁵ Embracing non-pain symptoms as part of the pain experience may lead to improved diagnostics and more client-centered interventions. QST can help identify individual challenges in daily life and suggest non-pharmacological approaches to manage pain more effectively (i.e., psychotherapy). QST may have future clinical utility but should be used in conjunction with other validated assessments and cannot replace a clinical interview. This approach broadens treatment options, particularly for those experiencing comorbid psychological distress, mental health disorders, and history of trauma which includes many individuals with chronic pain.