- Email: [email protected]
Quantitative sensory testing: A stimulating look at chronic pain
The Veterinary Journal 193 (2012) 315–316
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Guest Editorial
Quantitative sensory testing: A stimulating look at chronic pain
Quantitative sensory testing (QST) is a term used to describe different forms of psychophysical testing of skin, mucosa, or muscle tissue that assess sensory and pain perception pathways (Pavlakovic and Petzke, 2010), and typically include warm and cold perception, mechanical threshold testing and allodynia (pain due to a stimulus which does not normally induce pain). The basic premise of QST is that physical stimuli applied to the body under normal physiological conditions are transduced by activating specific sets of receptors (nociceptors) that send signals along specific anatomical components of the sensory nervous system. Such components include peripheral nerve fibers, as well as central pathways from the dorsal horn of the spinal cord to the thalamus and cortical structures relevant to sensory perception. All of these components contribute to pain perception and ultimately to the animal’s reaction to the physical properties of the stimulus (Backonja et al., 2009). It is important to address the misperception that QST is an ‘objective test for pain’. Nociception and pain are not the same. Nociception is the processing of noxious stimuli through the somatosensory system, whereas pain is the complex, multidimensional individual and subjective experience (Arendt-Nielsen and Yarnitsky, 2009). For example, paw-withdrawal latency from a mechanical stimulus gauges neuronal threshold activity but may have no direct correlation with the pain experienced by an animal (Arendt-Nielsen and Yarnitsky, 2009). In addition, QST is not ‘objective’ in the sense of being independent of perception (Backonja et al., 2009). QST is considered ‘semi-objective’ because factors such as cognitive deficits, inattention and anxiety can adversely influence pain perception and the response to a testing procedure (Backonja et al., 2009; Pavlakovic and Petzke, 2010). Despite its limitations, QST can provide valuable clinical information. In humans, QST plays a role in the diagnosis of neuropathic pain syndromes i.e. conditions in which there is primary dysfunction in the nervous system. Because of its ability to quantitate changes in somatosensory neural function, QST is used to tease out the mechanisms involved in the somatosensory abnormalities present in patients with conditions such as diabetic neuropathy, post herpetic neuralgia, and multiple sclerosis (Arendt-Nielsen and Yarnitsky, 2009; Backonja et al., 2009). In companion animals, pain behaviors expressed by dogs with syringomyelia or post amputation phantom limb pain suggest that they experience neuropathic pain associated with these conditions; however, QST will be far more applicable to clinical veterinary medicine if it has a role outside of neuropathic pain assessment alone (Grubb, 2010; Rusbridge and Jeffery, 2008). In an important article from the Cardiovascular Sciences group at the Royal (Dick) School of Veterinary Studies in Edinburgh, Dr. 1090-0233/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tvjl.2012.03.021
Nichola Brydges and her colleagues compare techniques for sensory assessment in dogs with chronic pain associated with musculoskeletal disease (Brydges et al., 2012). Pain following musculoskeletal injury is considered nociceptive rather than neuropathic. Nociceptive pain occurs through activation of nociceptors (peripheral sensory neurons in skin, muscle, joints and viscera) in response to a noxious stimulus, such as joint or muscle injury. Yet with progression from acute to chronic stages of disease, altered nociceptive processing, known as sensitization, can occur. Peripheral sensitization arises due to the action of inflammatory mediators released around the site of tissue damage, leading to a reduction in threshold and an increase in responsiveness of the nociceptors. This contributes to pain hypersensitivity found at the site of tissue damage. For example, blunt pressure on a muscle belly may (under normal circumstances) produce mild discomfort, yet at the site of a muscle strain can evoke sharp pain. Sustained activity in nociceptors can also cause an increase in the excitability of neurons within the CNS, such that normal inputs begin to produce abnormal responses. This central sensitization alters the strength of synaptic connections such that low-threshold sensory fibers begin to activate neurons in the spinal cord that normally only respond to noxious stimuli. As a result, an input that would normally evoke an innocuous sensation (such as a light touch of the skin) now produces pain. Due to sensitization, patients with chronic joint injury may present with signs typically associated with neuropathic injury (Courtney et al., 2010; Pavlakovic and Petzke, 2010). Such is the premise of the article by Brydges et al. (2012). While osteoarthritic pain is classically attributed to joint damage, sensitization can influence the chronic pain associated with this condition (Pavlakovic and Petzke, 2010). This helps explain the fact that the degree of radiologically-verified joint damage is not well correlated with the severity of pain and associated clinical signs. Documenting altered somatosensory processing in patients with chronic nociceptive pain (such as osteoarthritis) opens a wide range of opportunities for employing QST in clinical research and clinical practice. Ideally, QST will lead to better diagnosis and targeted management of chronic pain states. Based on QST evaluations, drugs traditionally used to treat neuropathic pain may be prescribed in conjunction with traditional management regimens e.g. pregabalin for musculoskeletal pain (Arendt-Nielsen and Yarnitsky, 2009; Pavlakovic and Petzke, 2010). QST could also be used as an outcome measure to document treatment-related changes in somatosensory function (Backonja et al., 2009). If treatment-related normalization of QST response is observed when clinical pain is reduced, QST measures may be developed as a sensitive index of treatment outcome (Backonja et al., 2009).
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Guest Editorial / The Veterinary Journal 193 (2012) 315–316
Based on these potential applications, it is tempting to suggest a standardized approach to QST for musculoskeletal pain in veterinary patients. However, there are many hurdles that must be overcome before QST becomes a valuable component of clinical practice or clinical research, not the least of which are the development of standards for testing, the accumulation of normative data, and the generation of consensus and guidelines documents on how to interpret the data (Backonja et al., 2009). Standardization of experimental protocols and environmental conditions under which the testing is performed is essential for obtaining reproducible results comparable to normative data and data from different testing centers (Pavlakovic and Petzke, 2010). The sensitivity and specificity of methods for the detection of specific pain disorders, the test– retest characteristics, and the influence of expectations of both the animal and the examiner need complete elucidation (Backonja et al., 2009). The opportunities for the use of QST in clinical veterinary medicine are great, but much more work is needed to develop easy-to-use, validated, and simple test paradigms. Future studies should use QST to collect more standardized data allowing the clinical phenotyping of large populations of animals with pain due to known disease etiologies. This approach should help to clarify the relationships between the etiology, the somatosensory abnormalities and the clinical signs of pain (Courtney et al., 2010). In addition, there needs to be education about the definitions and terms used in pain research and practice and improved understanding of what QST entails, the type of information that can be obtained, and what that information ultimately means.
Dorothy Cimino Brown Department of Clinical Studies, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA E-mail address: [email protected]
References Arendt-Nielsen, L., Yarnitsky, D., 2009. Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. Journal of Pain 10, 556–572. Backonja, M.-M., Walk, D., Edwards, R.R., Sehgal, N., Moeller-Bertram, T., Wasan, A., Irving, G., Argoff, C., Wallace, M., 2009. Quantitative sensory testing in measurement of neuropathic pain phenomena and other sensory abnormalities. Clinical Journal of Pain 25, 641–647. Brydges, N.M., Argyle, D.J., Mosley, J.R., Duncan, J.C., Fleetwood-Walker, S., Clements, D.N., 2012. Clinical assessments of increased sensory sensitivity in dogs with cranial cruciate ligament rupture. The Veterinary Journal 193, 545– 550. Courtney, C.A., Kavchak, A.E., Lowry, C.D., O’Hearn, M.A., 2010. Interpreting joint pain: Quantitative sensory testing in musculoskeletal management. Journal of Orthopaedic and Sports Physical Therapy 40, 818–825. Grubb, T., 2010. Chronic neuropathic pain in veterinary patients. Topics in Companion Animal Medicine 25, 45–52. Pavlakovic, G., Petzke, F., 2010. The role of quantitative sensory testing in the evaluation of musculoskeletal pain conditions. Current Rheumatology Reports 12, 455–461. Rusbridge, C., Jeffery, N.D., 2008. Pathophysiology and treatment of neuropathic pain associated with syringomyelia. The Veterinary Journal 175, 164–172.
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Guest Editorial
Quantitative sensory testing: A stimulating look at chronic pain
Quantitative sensory testing (QST) is a term used to describe different forms of psychophysical testing of skin, mucosa, or muscle tissue that assess sensory and pain perception pathways (Pavlakovic and Petzke, 2010), and typically include warm and cold perception, mechanical threshold testing and allodynia (pain due to a stimulus which does not normally induce pain). The basic premise of QST is that physical stimuli applied to the body under normal physiological conditions are transduced by activating specific sets of receptors (nociceptors) that send signals along specific anatomical components of the sensory nervous system. Such components include peripheral nerve fibers, as well as central pathways from the dorsal horn of the spinal cord to the thalamus and cortical structures relevant to sensory perception. All of these components contribute to pain perception and ultimately to the animal’s reaction to the physical properties of the stimulus (Backonja et al., 2009). It is important to address the misperception that QST is an ‘objective test for pain’. Nociception and pain are not the same. Nociception is the processing of noxious stimuli through the somatosensory system, whereas pain is the complex, multidimensional individual and subjective experience (Arendt-Nielsen and Yarnitsky, 2009). For example, paw-withdrawal latency from a mechanical stimulus gauges neuronal threshold activity but may have no direct correlation with the pain experienced by an animal (Arendt-Nielsen and Yarnitsky, 2009). In addition, QST is not ‘objective’ in the sense of being independent of perception (Backonja et al., 2009). QST is considered ‘semi-objective’ because factors such as cognitive deficits, inattention and anxiety can adversely influence pain perception and the response to a testing procedure (Backonja et al., 2009; Pavlakovic and Petzke, 2010). Despite its limitations, QST can provide valuable clinical information. In humans, QST plays a role in the diagnosis of neuropathic pain syndromes i.e. conditions in which there is primary dysfunction in the nervous system. Because of its ability to quantitate changes in somatosensory neural function, QST is used to tease out the mechanisms involved in the somatosensory abnormalities present in patients with conditions such as diabetic neuropathy, post herpetic neuralgia, and multiple sclerosis (Arendt-Nielsen and Yarnitsky, 2009; Backonja et al., 2009). In companion animals, pain behaviors expressed by dogs with syringomyelia or post amputation phantom limb pain suggest that they experience neuropathic pain associated with these conditions; however, QST will be far more applicable to clinical veterinary medicine if it has a role outside of neuropathic pain assessment alone (Grubb, 2010; Rusbridge and Jeffery, 2008). In an important article from the Cardiovascular Sciences group at the Royal (Dick) School of Veterinary Studies in Edinburgh, Dr. 1090-0233/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tvjl.2012.03.021
Nichola Brydges and her colleagues compare techniques for sensory assessment in dogs with chronic pain associated with musculoskeletal disease (Brydges et al., 2012). Pain following musculoskeletal injury is considered nociceptive rather than neuropathic. Nociceptive pain occurs through activation of nociceptors (peripheral sensory neurons in skin, muscle, joints and viscera) in response to a noxious stimulus, such as joint or muscle injury. Yet with progression from acute to chronic stages of disease, altered nociceptive processing, known as sensitization, can occur. Peripheral sensitization arises due to the action of inflammatory mediators released around the site of tissue damage, leading to a reduction in threshold and an increase in responsiveness of the nociceptors. This contributes to pain hypersensitivity found at the site of tissue damage. For example, blunt pressure on a muscle belly may (under normal circumstances) produce mild discomfort, yet at the site of a muscle strain can evoke sharp pain. Sustained activity in nociceptors can also cause an increase in the excitability of neurons within the CNS, such that normal inputs begin to produce abnormal responses. This central sensitization alters the strength of synaptic connections such that low-threshold sensory fibers begin to activate neurons in the spinal cord that normally only respond to noxious stimuli. As a result, an input that would normally evoke an innocuous sensation (such as a light touch of the skin) now produces pain. Due to sensitization, patients with chronic joint injury may present with signs typically associated with neuropathic injury (Courtney et al., 2010; Pavlakovic and Petzke, 2010). Such is the premise of the article by Brydges et al. (2012). While osteoarthritic pain is classically attributed to joint damage, sensitization can influence the chronic pain associated with this condition (Pavlakovic and Petzke, 2010). This helps explain the fact that the degree of radiologically-verified joint damage is not well correlated with the severity of pain and associated clinical signs. Documenting altered somatosensory processing in patients with chronic nociceptive pain (such as osteoarthritis) opens a wide range of opportunities for employing QST in clinical research and clinical practice. Ideally, QST will lead to better diagnosis and targeted management of chronic pain states. Based on QST evaluations, drugs traditionally used to treat neuropathic pain may be prescribed in conjunction with traditional management regimens e.g. pregabalin for musculoskeletal pain (Arendt-Nielsen and Yarnitsky, 2009; Pavlakovic and Petzke, 2010). QST could also be used as an outcome measure to document treatment-related changes in somatosensory function (Backonja et al., 2009). If treatment-related normalization of QST response is observed when clinical pain is reduced, QST measures may be developed as a sensitive index of treatment outcome (Backonja et al., 2009).
316
Guest Editorial / The Veterinary Journal 193 (2012) 315–316
Based on these potential applications, it is tempting to suggest a standardized approach to QST for musculoskeletal pain in veterinary patients. However, there are many hurdles that must be overcome before QST becomes a valuable component of clinical practice or clinical research, not the least of which are the development of standards for testing, the accumulation of normative data, and the generation of consensus and guidelines documents on how to interpret the data (Backonja et al., 2009). Standardization of experimental protocols and environmental conditions under which the testing is performed is essential for obtaining reproducible results comparable to normative data and data from different testing centers (Pavlakovic and Petzke, 2010). The sensitivity and specificity of methods for the detection of specific pain disorders, the test– retest characteristics, and the influence of expectations of both the animal and the examiner need complete elucidation (Backonja et al., 2009). The opportunities for the use of QST in clinical veterinary medicine are great, but much more work is needed to develop easy-to-use, validated, and simple test paradigms. Future studies should use QST to collect more standardized data allowing the clinical phenotyping of large populations of animals with pain due to known disease etiologies. This approach should help to clarify the relationships between the etiology, the somatosensory abnormalities and the clinical signs of pain (Courtney et al., 2010). In addition, there needs to be education about the definitions and terms used in pain research and practice and improved understanding of what QST entails, the type of information that can be obtained, and what that information ultimately means.
Dorothy Cimino Brown Department of Clinical Studies, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA E-mail address: [email protected]
References Arendt-Nielsen, L., Yarnitsky, D., 2009. Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. Journal of Pain 10, 556–572. Backonja, M.-M., Walk, D., Edwards, R.R., Sehgal, N., Moeller-Bertram, T., Wasan, A., Irving, G., Argoff, C., Wallace, M., 2009. Quantitative sensory testing in measurement of neuropathic pain phenomena and other sensory abnormalities. Clinical Journal of Pain 25, 641–647. Brydges, N.M., Argyle, D.J., Mosley, J.R., Duncan, J.C., Fleetwood-Walker, S., Clements, D.N., 2012. Clinical assessments of increased sensory sensitivity in dogs with cranial cruciate ligament rupture. The Veterinary Journal 193, 545– 550. Courtney, C.A., Kavchak, A.E., Lowry, C.D., O’Hearn, M.A., 2010. Interpreting joint pain: Quantitative sensory testing in musculoskeletal management. Journal of Orthopaedic and Sports Physical Therapy 40, 818–825. Grubb, T., 2010. Chronic neuropathic pain in veterinary patients. Topics in Companion Animal Medicine 25, 45–52. Pavlakovic, G., Petzke, F., 2010. The role of quantitative sensory testing in the evaluation of musculoskeletal pain conditions. Current Rheumatology Reports 12, 455–461. Rusbridge, C., Jeffery, N.D., 2008. Pathophysiology and treatment of neuropathic pain associated with syringomyelia. The Veterinary Journal 175, 164–172.