Indian Journal of Pain

ORIGINAL ARTICLE
Year
: 2021  |  Volume : 35  |  Issue : 3  |  Page : 203--208

Impact of central sensitization on pain intensity, pain-related symptoms, and health-related quality of life in chronic pain outpatient department


Deep Divanshu Lall, Rajat Gupta, Nandini Dadu, Ashu Jain 
 Department of Pain Medicine and Palliative Care, Artemis Hospitals, Gurugram, Haryana, India

Correspondence Address:
Dr. Deep Divanshu Lall
135, 2nd Floor, Pocket D-12, Sector- 8, Rohini, Delhi
India

Abstract

Context: Central sensitization (CS) has been proposed as a common underlying pathophysiology to explain poorly understood pain-related syndromes. This is termed under central sensitivity syndromes (CSSs), for which no specific organic cause has been found. Aims: The aim of the present study was to investigate whether there is an association between the CS Inventory (CSI) score, pain-related symptoms, pain-related disability, health-related quality of life (QOL), and poorly understood pain-related syndromes and whether they differed by disease type. This study also evaluated the association between severity of CS and the associated CSSs. Methods: A total of seventy patients who attended a pain clinic (chronic pain outpatient department) were assessed randomly. CSI score, CSSs, EuroQOL-5 Dimension-5 Level, Brief Pain Inventory, and Fibromyalgia (FM) Severity Scale were assessed and compared. Statistical Analysis: Univariate correlation analysis was performed in each group to evaluate: (1) severity of CS, (2) presence/absence of CSSs, (3) pain intensity and pain interference, and (4) CSI score and FM Severity Scale. Results: CSI score has a significant association with CSSs, pain-related symptoms such as pain/discomfort, anxiety/depression, mood, and sleep. Conclusions: In our study, CS has been shown to have a significant impact on mean pain score and QOL by strongly impacting mobility, mood, and sleep. CS is the underlying root cause of various CSSs. This study concludes that CS should be evaluated as a routine in all chronic pain patients.



How to cite this article:
Lall DD, Gupta R, Dadu N, Jain A. Impact of central sensitization on pain intensity, pain-related symptoms, and health-related quality of life in chronic pain outpatient department.Indian J Pain 2021;35:203-208


How to cite this URL:
Lall DD, Gupta R, Dadu N, Jain A. Impact of central sensitization on pain intensity, pain-related symptoms, and health-related quality of life in chronic pain outpatient department. Indian J Pain [serial online] 2021 [cited 2022 Jan 28 ];35:203-208
Available from: https://www.indianjpain.org/text.asp?2021/35/3/203/334099


Full Text



 Introduction



The International Association for the Study of Pain defines central sensitization (CS) as an increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold afferent input.[1] The International Association for the Study of Pain defines nociplastic pain as pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain. The presence of CS has been demonstrated in central sensitivity syndrome (CSS) populations by comparing the pain thresholds of CSS patients to the thresholds of pain-free controls to various stimuli (such as electrical, pressure, cold, and heat). Objective measures of CS, which complement subjective self-report, include brain imaging and nociceptive spinal reflex tests. CS has been proposed as the root etiology for CSSs which refer to a group of medically indistinct disorders for which no organic cause can be found. These include fibromyalgia (FM), chronic fatigue syndrome, irritable bowel syndrome (IBS), temporomandibular joint disorder (TMD), and tension headache/migraine, among others. These CSSs are highly intercorrelated, share many common symptoms, including pain, and all demonstrate evidence of CS. Not all chronic pain patients have CS, but it may underlie subgroups of patients with chronic low back pain (CLBP), whiplash, osteoarthritis, rheumatoid arthritis, tennis elbow pain, shoulder pain, and headache.[6],[14],[15],[16],[18],[23] If present, CS may dominate the clinical picture, modulate the transition to chronicity,[22],[23] and mediate treatment responses.[13],[17] CS encompasses various related dysfunctions within the central nervous system, including altered sensory processing in the brain, with increased brain activity in areas known to be involved in acute pain sensations (insula, anterior cingulate cortex, and prefrontal cortex), as well as in regions not involved in acute pain sensations (various brain stem nuclei, dorsolateral frontal cortex, and parietal associated cortex). Research findings also suggest a specific role of the brain stem for the maintenance of CS in humans.[19] Furthermore, long-term potentiation of neuronal synapses in the anterior cingulate cortex,[20] nucleus accumbens, insula, and the sensorimotor cortex, as well as decreased gamma-aminobutyric acid neurotransmission,[21] represent two potential mechanisms contributing to the overactive pain neuromatrix. This can lead to poor functioning of descending antinociceptive mechanisms and increased activity of brain-orchestrated nociceptive facilitatory pathways. It has been suggested that changes in central pain processing in some individuals with regional pain can result in the later development of chronic widespread pain.[4] CS Inventory (CSI) is intended as a screening instrument to help identify the presence of a CSS, and to alert clinicians that presenting symptoms may be related to CS. Therefore, this study was conducted to evaluate an impact of CS on pain intensity, pain-related symptoms, and health-related quality of life (QOL) in chronic pain outpatient department.

Aim of the study

To analyze the association among CSI score, PI, pain-related symptoms, pain interference, health-related QOL (HRQOL), and FM Severity ScaleTo evaluate the severity of CS and associated CSSs.

 Methods



Seventy participants visiting chronic outpatient department were included in this study on a random basis in an institutional-based unicentric prospective observational study.

CSI (Parts A and B), HRQOL EuroQOL-5 Dimension-5 Level (EQ-5D-5 L) Questionnaire, Brief Pain Inventory (BPI), and FM Severity Scale were used.

We evaluated the area under the curve in each analysis to identify:

Severity of CSPresence/absence of CSSsPI and pain interferenceCSI score and FM Severity Scale.

Inclusion criterion

Complaints of pain more than 3 monthsAge between 20 and 70 yearsAssessment of patients with complaint of nonmalignant chronic pain was done.

Exclusion criterion

Presence of a postoperative conditionSerious pathologies (unhealed fractures, tumors, acute trauma, or serious illness)History of central nervous system diseaseDiagnosed psychiatric disorders (e.g., schizophrenia, bipolar disorder, or somatoform disorder) as diagnosed by a psychiatristPatients who did not give consent.

Measures

Demographic and clinical characteristics

Demographic data (age, sex, weight, height, education level, and duration of symptoms) and clinical characteristics were assessed in participants those who fit in inclusion criterion using self-reported measures. The CSI consists of two parts: A and B.[27] Part A is a 25-item self-report questionnaire designed to assess health-related symptoms that are common in CSSs. Each item is rated on a 5-point Likert-type scale (0 = never and 4 = always), with total scores of 0–100. Part B (which is not scored) is designed to determine whether one or more specific disorders, including seven separate CSSs, have been previously diagnosed (restless leg syndrome, chronic fatigue syndrome, FM, TMD, migraine or tension headaches, IBS, multiple chemical sensitivities, neck injuries [including whiplash], anxiety or panic attacks, and depression). HRQOL was measured using the EQ-5D-5 L. The EQ-5D-5 L was developed as a nondisease-specific instrument but has been standardized and can be used as a complement to existing HRQOL measures. It comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five levels of severity (no problem, slight problem, moderate problem, severe problem, and unable/extreme problem), which can generate a single index value for each health state. These are numerical values on a scale, with 1 denoting full health and 0 denoting death. The EQ Visual Analog Scale (VAS) records the respondent's overall current health on a vertical VAS, where the endpoints are labeled “the best health you can imagine” and “the worst health you can imagine.” The EQ VAS provides a quantitative measure of the patient's perception of their overall health.[28]

Pain intensity and pain interference were measured using the BPI.[29] It consists of four pain intensity and seven pain interference items. These items are presented on 0–10 scales, with 0 = no and 10 = worst (completely). From these, individual pain intensity and pain interference scores are calculated by averaging. The validation and clinical utility of the BPI has been evaluated for several disorders.[27] In addition, we used the FM Severity Scale that consists of Widespread Pain Index (WPI) and Symptom Severity score (SS score 2a and b), originally developed for patients with FM, to count the number of painful sites.[30] The WPI results in an overall score of 0–19 points, provided by the number of up to 19 specific areas where the patient experienced pain over the previous week. ACR 2016[30] added “generalized pain criterion to insure that regional pain syndromes are not captured by the criteria.” This criterion is pain in at least four of five regions. Five regions are four quadrants plus one axial: left upper region – jaw, shoulder girdle, upper arm, and lower arm; right upper region – jaw, shoulder girdle, upper arm, and lower arm; left lower region – hip (buttock and trochanter), upper leg, and lower leg; right lower region – hip (buttock and trochanter), upper leg, and lower leg; and axial region – neck, upper back, lower back, chest, and abdomen. Somatic Symptom (SS) Scale score: For each of the three symptoms below, indicate the level of severity over the past week using the following scale: 0 = no problem, 1 = slight or mild problems, generally mild or intermittent, 2 = moderate, considerable problems, often present and/or at a moderate level, 3 = severe: pervasive, continuous, life-disturbing problems. Symptoms: fatigue, waking unrefreshed, cognitive symptoms. The SS Scale score is the sum of the severity of the three symptoms (fatigue, waking unrefreshed, and cognitive symptoms) plus the extent (severity) of SS in general. The final score is between 0 and 12. A patient meets the diagnostic criterion for FM if the following three conditions are met: 1a. The WPI score (Part 1) is ≥7 AND the SS score (Part 2a and b) is ≥5.

OR

b. The WPI score (Part 1) is from 3 to 6 AND SS score (Part 2a and b) is ≥9Symptoms have been present at a similar level for at least 3 monthsYou do not have any disorder that would otherwise explain the pain.

 Results



A total of seventy patients who attended chronic pain outpatient department were assessed randomly in this study: female – 40 (57.1%) and male – 30 (42.9%). [Table 1] shows the summary of measurements. Regarding pain-related outcomes, there were no significant differences in pain intensity and pain interference scores between different groups (P = 0.16 and P = 0.36, respectively), as shown in [Table 1]. The CSI score was significantly higher in the patients with complaints of neck pain and headache and generalized body pain (P = 0.04), as shown in [Table 1]. The mean score of CSSs was higher in patients with complaint of generalized body pain (P = 0.01), as shown in [Table 1]. The proportion of participants who were diagnosed with one or more CSSs was higher in generalized body pain (P = 0.02), as shown in [Table 2]. CSI score has a significant association with mean pain score (r = 0.3, P = 0.01) and duration of symptoms (r = 0.4, P < 0.001); CSI score has a significant association with CSS (r = 0.5, P < 0.001). The number of syndromes and the percentage of patients increased with increase in the severity of CS (P < 0.001); CSI score has an inverse association with FM severity score (r = 0.5, P < 0.001), as shown in [Table 3].{Table 1}{Table 2}{Table 3}

CSI score has a significant association with utility coefficient derived from HRQOL (r = –0.4, P < 0.001). CSI score has a significant association only with mobility (r = 0.3, P = 0.03) out of five pain-related disabilities (mobility, self-care, usual activities, relationship with other people, and enjoyment of life). CSI score has a significant association with pain-related symptoms such as pain/discomfort, anxiety/depression, mood, and sleep (P = 0.005, P < 0.001, P = 0.01, and P = 0.02, respectively). CSI score has a significant association with pain interference calculated from BPI (P = 0.002), though there was no significant difference between different groups of patients.

The number of CSSs and the percentage of patients having CSS increased with increase in severity of CS except in patients of severe CS. As shown in [Table 2], 7.5% (4 patients out of 30) of patients in subclinical CS had CSS and maximum two CSSs were reported by one patient. Among patients having mild CS, 50% (12 out of 24) had CSSs and maximum three CSSs were reported by one patient. Among patients having moderate CS, 66.6% (4 out of 6) of patients had CSS and maximum six CSSs were reported by one patient. Among patients having severe CS, 50% (4 patients out of 8 patients) had CSS and maximum three CSSs were reported in two patients each.

Among patients having extreme CS, 100% of patients (2 patients out of 2) had CSSs and maximum seven CSSs were reported, as shown in [Table 4].{Table 4}

 Discussion



The aim of the present study was to investigate whether there is an association between the CSI score, pain-related symptoms, pain-related disability, HRQOL, and poorly understood pain-related syndromes and whether they differed by disease type and to evaluate the severity of CS and associated CSSs.

We found that the CSI score was significantly higher in the patients with complaints of neck pain and headache and generalized body pain (P = 0.04). The mean score of CSSs was higher in patients with complaint of generalized body pain (P = 0.01). A higher mean pain score in chronic pain may have been associated higher CSI score. CS probably occurs over a continuum, from a minor to a great extent. Therefore, it may be considered a basic characteristic of the disease. CS significantly affects QOL. Pain-related symptoms, such as pain/discomfort, anxiety/depression, mood, and sleep, are significantly interfered in patients having higher CSI score. Evaluation of CS helps us in treating the unexplainable symptoms associated with complaints of patients. Evaluation of CS also helps us in avoiding unnecessary imaging and cross-referrals and providing better patient education and reassurance. The presence of CS implies that the brain produces pain, fatigue, and other warning signs even when there is no real tissue damage. CS is not a disorder of the mind but rather a disease of the brain and spinal cord. Hence, the brain should become an important treatment target.[12] Evaluation of CS also helps in finding the associated overlapping CSSs. A higher CSI score is associated with higher numerical value of CSSs. A study conducted by Akira Mibu et al.[28] found that patients with CLBP showed more pronounced CS-related symptoms and higher prevalence of CSSs compared to the patients with knee osteoarthritis (KOA), and pain-related disability and HRQOL were associated with the CSI in both CLBP and KOA. Evaluating CSI and its impact on pain intensity, pain-related symptoms, and health-related QOL was the similarity when compared with our study. Our study was different from a study conducted by Akira Mibu et al.,[28] as we have evaluated CS in the abovementioned various subsets of patients including low back pain and KOA. In our study also, CS score and its impact ranked on a higher side in patients of low back pain after neck pain with headache and generalized body pain. There was not much literature found correlating to our topic.

 Conclusion



In our study, CS has been shown to have a significant impact on mean pain score and QOL by strongly impacting mobility, mood, and sleep. CS is the underlying root cause of various CSSs. This study concludes that CS should be evaluated as a routine in all chronic pain patients

Limitations

This study's limitations should be considered when interpreting the result. Small sample size may affect the results of the study. Further research comprising large sample size is required to find out the impact of CS on chronic outpatients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Mayer TG, Neblett R, Cohen H, Howard KJ, Choi YH, Williams MJ, et al. The development and psychometric validation of the central sensitization inventory. Pain Pract 2012;12:276-85.
2Kindler LL, Bennett RM, Jones KD. Central sensitivity syndromes: Mounting pathophysiologic evidence to link fibromyalgia with other common chronic pain disorders. Pain Manag Nurs 2011;12:15-24.
3Neblett R, Cohen H, Choi Y, Hartzell MM, Williams M, Mayer TG, et al. The Central Sensitization Inventory (CSI): Establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample. J Pain 2013;14:438-45.
4Robinson JP, Theodore BR, Wilson HD, Waldo PG, Turk DC. Determination of fibromyalgia syndrome after whiplash injuries: Methodologic issues. Pain 2011;152:1311-6.
5Robinson ME, Craggs JG, Price DD, Perlstein WM, Staud R. Gray matter volumes of pain-related brain areas are decreased in fibromyalgia syndrome. J Pain 2011;12:436-43.
6Smart KM, Blake C, Staines A, Doody C. The discriminative validity of “nociceptive,” “peripheral neuropathic,” and “central sensitization” as mechanisms-based classifications of musculoskeletal pain. Clin J Pain 2011;27:655-63.
7Van Houdenhove B, Luyten P. Central sensitivity syndromes: Stress system failure may explain the whole picture. Semin Arthritis Rheum 2009;39:218-9.
8Yunus MB. Central sensitivity syndromes: A unified concept for fibromyalgia and other similar maladies. J Indian Rheumatol Assoc 2000;8:27-33.
9Yunus MB. Fibromyalgia and overlapping disorders: The unifying concept of central sensitivity syndromes. Semin Arthritis Rheum 2007;36:339-56.
10Yunus MB. Role of central sensitization in symptoms beyond muscle pain, and the evaluation of a patient with widespread pain. Best Pract Res Clin Rheumatol 2007;21:481-97.
11Roberts A, Lorduy K, Gatchel RJ. Central sensitization: Common etiology in somatoform disorders. Practical Pain Management 2013;13. Available from: https://www.practicalpainmanagement.com/pain/central-sensitization-common-etiology-somatoform-disorders. [Last accessed on 2021 Dec 01].
12Nijs J, Torres-Cueco R, van Wilgen CP, Girbes EL, Struyf F, Roussel N, et al. Applying modern pain neuroscience in clinical practice: Criteria for the classification of central sensitization pain. Pain Physician 2014;17:447-57.
13Jull G, Sterling M, Kenardy J, Beller E. Does the presence of sensory hypersensitivity influence outcomes of physical rehabilitation for chronic whiplash? A preliminary RCT. Pain 2007;129:28-34.
14Staud R. Evidence for shared pain mechanisms in osteoarthritis, low back pain, and fibromyalgia. Curr Rheumatol Rep 2011;13:513-20.
15Paul TM, Soo Hoo J, Chae J, Wilson RD. Central hypersensitivity in patients with subacromial impingement syndrome. Arch Phys Med Rehabil 2012;93:2206-9.
16Buchgreitz L, Egsgaard LL, Jensen R, Arendt-Nielsen L, Bendtsen L. Abnormal pain processing in chronic tension-type headache: A high-density EEG brain mapping study. Brain 2008;131:3232-8.
17Coombes BK, Bisset L, Vicenzino B. Thermal hyperalgesia distinguishes those with severe pain and disability in unilateral lateral epicondylalgia. Clin J Pain 2012;28:595-601.
18Nijs J, Van Houdenhove B, Oostendorp RA. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Man Ther 2010;15:135-41.
19Lee MC, Zambreanu L, Menon DK, Tracey I. Identifying brain activity specifically related to the maintenance and perceptual consequence of central sensitization in humans. J Neurosci 2008;28:11642-9.
20Zhuo M. A synaptic model for pain: Long-term potentiation in the anterior cingulate cortex. Mol Cells 2007;23:259-71.
21Suarez-Roca H, Leal L, Silva JA, Pinerua-Shuhaibar L, Quintero L. Reduced GABA neurotransmission underlies hyperalgesia induced by repeated forced swimming stress. Behav Brain Res 2008;189:159-69.
22Baliki MN, Petre B, Torbey S, Herrmann KM, Huang L, Schnitzer TJ, et al. Corticostriatal functional connectivity predicts transition to chronic back pain. Nat Neurosci 2012;15:1117-9.
23Smart KM, Blake C, Staines A, Thacker M, Doody C. Mechanisms-based classifications of musculoskeletal pain: Part 1 of 3: Symptoms and signs of central sensitisation in patients with low back (± leg) pain. Man Ther 2012;17:336-44.
24Neblett R, Hartzell MM, Cohen H, Mayer TG, Williams M, Choi Y, et al. Ability of the central sensitization inventory to identify central sensitivity syndromes in an outpatient chronic pain sample. Clin J Pain 2015;31:323-32.
25Scerbo T, Colasurdo J, Dunn S, Unger J, Nijs J, Cook C. Measurement properties of the central sensitization inventory: A systematic review. Pain Pract 2018;18:544-54.
26Sterling M, Jull G, Vicenzino B, Kenardy J. Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery. Pain 2003;104:509-17.
27Mibu A, Nishigami T, Tanaka K, Manfuku M, Yono S. Difference in the impact of central sensitization on pain-related symptoms between patients with chronic low back pain and knee osteoarthritis. J Pain Res 2019;12:1757-65.
28Oemar M, Janssen B. EQ-5D-5L User Guide: Basic Information on How to Use the EQ-5D-5L Instrument. Rotterdam: EuroQol Group; 2013.
29Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain 2008;9:105-21.
30J.SEMARTHRIT 2016 Revisions to the 2010/2011 Fibromyalgia Diagnostic Criteria. Available from: https://doi.org/10.1016/J.SEMARTHRIT.2016.08.012. [Last accessed on 2021 Oct 01]