Highlights
- •Compared with controls, about twice as many adults with SCD showed sensitization.
- •Of those with sensitization, more than half exhibited some central sensitization.
- •Sensitization was associated with frequent pain crisis episodes among SCD patients.
- •Persistent allodynia and hyperalgesia can be part of the SCD pain experience.
- •Neuropathic pain, if part of SCD pain, should be appropriately assessed and treated.
Abstract
Evidence supports, but is inconclusive that sensitization contributes to chronic pain in some adults
with sickle cell disease (SCD). We determined the prevalence of pain sensitization
among adults with SCD pain compared with pain-free healthy adults. In a cross sectional,
single session study of 186 African American outpatients with SCD pain (age 18–74
years, 59% female) and 124 healthy age, gender, and race matched control subjects
(age 18–69 years, 49% female), we compared responses to standard thermal (Medoc TSA
II) and mechanical stimuli (von Frey filaments). Although we observed no significant
differences in thermal thresholds between controls and patients, patients with SCD
had lower pain thresholds to mechanical stimuli and reported higher pain intensity
scores to all thermal and mechanical stimuli at a non-painful body site. Compared
with controls, about twice as many patients with SCD showed sensitization: 12% versus
23% at the anterior forearm site (P = .02), and 16% versus 32% across 3 tested sites (P = .004). Among patients with SCD, 18% exhibited some element of central sensitization.
Findings indicate that persistent allodynia and hyperalgesia can be part of the SCD
pain experience and should be considered when selecting therapies for SCD pain.
Perspective
Compared with matched healthy controls, quantitative sensory testing in adults with
pain and sickle cell disease (SCD) demonstrates higher prevalence of sensitization,
including central sensitization. The findings of allodynia and hyperalgesia may indicate
neuropathic pain and could contribute to a paradigm shift in assessment and treatment
of SCD pain.
Key words
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References
- Sickle Cell Pain.2nd ed. Lippincott Williams & Wilkins, Philadelphia2015
- Sickle cell pain: a critical reappraisal.Blood. 2012; 120: 3647-3656
- Cellular and molecular mechanisms of pain.Cell. 2009; 139: 267-284
- Guidelines for the Management of Acute and Chronic Pain in Sickle-cell Disease.American Pain Society, Glenview, IL1999
- Early insights into the neurobiology of pain in sickle cell disease: a systematic review of the literature.Pediatr Blood Cancer. 2015; 62: 1501-1511
- Patients with sickle cell disease have increased sensitivity to cold and heat.Am J Hematol. 2013; 88: 37-43
- Quantitative sensory testing and pain-evoked cytokine reactivity: Comparison of patients with sickle cell disease to healthy matched controls.Pain. 2016; 157: 949-956
- An evaluation of central sensitization in patients with sickle cell disease.J Pain. 2016; 17: 617-627
- Chronic opioid therapy and central sensitization in sickle cell disease.Am J Prev Med. 2016; 51: S69-S77
- The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons.Nat Neurosci. 2012; 15: 1015-1021
Cruccu G, Sommer C, Anand P, Attal N, Baron R, Garcia-Larrea L, Haanpaa M, Jensen TS, Serra J, Treede RD. EFNS guidelines on neuropathic pain assessment: Revised 2009. Eur J Neurol. 17:1010-1018, 2010
- Safety and utility of quantitative sensory testing among adults with sickle cell disease: Indicators of neuropathic pain.Pain Pract. 2016; 16: 282-293
- Postherpetic neuralgia: Irritable nociceptors and deafferentation.Neurobiol Dis. 1998; 5: 209-227
- Diagnosis and management of neuropathic pain.BMJ. 2009; 339: b3002
- Sickle cell mice exhibit mechanical allodynia and enhanced responsiveness in light touch cutaneous mechanoreceptors.Mol Pain. 2012; 8: 62
- Experimental pain sensitivity and reports of negative thoughts in adults with sickle-cell disease.Behav Ther. 1995; 26: 273-293
- Effects of cognitive coping skills training on coping strategies and experimental pain sensitivity in African American adults with sickle cell disease.Health Psychol. 1996; 15: 3-10
- CaMKIIalpha underlies spontaneous and evoked pain behaviors in Berkeley sickle cell transgenic mice.Pain. 2016; 157: 2798-2806
- PKCdelta-targeted intervention relieves chronic pain in a murine sickle cell disease model.J Clin Invest. 2016; 126: 3053-3057
- Transient receptor potential vanilloid 1 mediates pain in mice with severe sickle cell disease.Blood. 2011; 118: 3376-3383
- Sensory and thermal quantitative testing in children with sickle cell disease.J Pediatr Hematol Oncol. 2015; 37: 185-189
- The development and preliminary validation of an insrument to assess patients' attitudes toward pain.J Psychosom Res. 1987; 31: 393-400
- Molecular mechanisms of nociception.Nature. 2001; 413: 203-210
- Patient reports of health outcome for adults living with sickle cell disease: Development and testing of the ASCQ-Me item banks.Health Qual Life Outcomes. 2014; 12: 125
- Pain ratings at the thresholds are necessary for interpretation of quantitative sensory testing.Muscle Nerve. 2005; 32: 179-184
- Gender differences in pain and healthcare utilization for adult sickle cell patients: the PiSCES Project.J Womens Health (Larchmt). 2006; 15: 146-154
- Presence of neuropathic pain as an underlying mechanism for pain associated with cold weather in patients with sickle cell disease.Med Hypotheses. 2011; 77: 491-493
- Mechanism-driven phase I translational study of trifluoperazine in adults with sickle cell disease.Eur J Pharmacol. 2014; 723: 419-424
- Measurement of pain: a comparison of the visual analogue with a nonvisual scale.Clin J Pain. 1987; 3: 197-199
- Thermal pain and sensory processing in children with sickle cell disease.Clin J Pain. 2014; 30: 244-250
- Thermal and mechanical quantitative sensory testing values among healthy African American adults.J Pain Res. 2019; 12: 2511-2527
- Neuronal transient receptor potential (TRP) channels and noxious sensory detection in sickle cell disease.Neurosci Lett. 2018; 694: 184-191
- Chemokine (c-c motif) receptor 2 mediates mechanical and cold hypersensitivity in sickle cell disease mice.Pain. 2018; 159: 1652-1663
- Management of sickle cell pain using pregabalin: A pilot study.Pain Manag Nurs. 2017; 18: 391-400
- A novel tool for the assessment of pain: Validation in low back pain.PLoS Med. 2009; 6e1000047
- Daily assessment of pain in adults with sickle cell disease.Ann Intern Med. 2008; 148: 94-101
- Classification of Chronic Pain, Second Edition (Revised).IASP Press, Washington, D.C.2011 (Available at)https://www.iasp-pain.org/PublicationsNews/Content.aspx?ItemNumber=1673Date accessed: October 25, 2019
- The word-graphic rating scale as a measure of children's and adolescents' pain intensity.Res Nurs Health. 1991; 14: 361-371
- Deconstructing the neuropathic pain phenotype to reveal neural mechanisms.Neuron. 2012; 73: 638-652
- Neurobiological mechanisms of pain in sickle cell disease.Hematol/Educ Program Am Soc Hematol. 2010; 2010: 403-408
- Cancer pain intensity measurement: Concurrent validity of three tools–finger dynamometer, pain intensity number scale, visual analogue scale.Hosp J. 1990; 6: 1-13
- Behavior of patients with lung cancer: description and associations with oncologic and pain variables.Pain. 1992; 51: 231-240
- Patient-reported outcomes: nociceptive and neuropathic pain and pain barriers in adult outpatients with sickle cell disease.J Natl Med Assoc. 2010; 102: 18-27
- Composite pain index: reliability, validity, and sensitivity of a patient-reported outcome for research.Pain Med. 2015; 16: 1341-1348
- Animal models of chronic pain: chronic post-ischemia pain: a novel animal model of complex regional pain syndrome type I produced by prolonged hindpaw ischemia and reperfusion in the rat.J Pain. 2004; 5: S1
- The prevalence of neuropathic pain: Clinical evaluation compared with screening tools in a community population.Pain Med. 2009; 10: 586-593
- Cold hypersensitivity increases with age in mice with sickle cell disease.Pain. 2014; 155: 2476-2485
Article info
Publication history
Published online: November 13, 2019
Accepted:
November 1,
2019
Received in revised form:
October 29,
2019
Received:
July 15,
2019
Footnotes
Disclosures: The authors report no conflicts of interest associated with this research. The study was supported by grant number R01HL124945 from the National Institutes of Health, National Heart Lung & Blood Institute (NHLBI) and T32AG049673 from the National Institutes of Aging (NIA). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NHLBI, NIA or Veteran's Administration. The final peer-reviewed manuscript is subject to the National Institutes of Health Public Access Policy.
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© 2019 by United States Association for the Study of Pain, Inc.
