Abstract
Chronic pain in persons living with HIV (PLWH) may be related to alterations in endogenous pain modulatory processes (e.g., high facilitation and low inhibition of nociception) that promote exaggerated pain responses, known as hyperalgesia, and central nervous system (CNS) sensitization. This observational study examined differences in endogenous pain modulatory processes between 59 PLWH with chronic pain, 51 PLWH without chronic pain, and 50 controls without HIV or chronic pain. Quantitative sensory testing for temporal summation (TS) of mechanical and heat pain as well as conditioned pain modulation (CPM) were used to assess endogenous pain facilitatory and inhibitory processes, respectively. Associations among TS, CPM, and self-reported clinical pain severity were also examined in PLWH with chronic pain. Findings demonstrated significantly greater TS of mechanical and heat pain for PLWH with chronic pain compared to PLWH without chronic pain and controls. CPM effects were present in controls, but not in either PLWH with or without chronic pain. Among PLWH with chronic pain, greater TS of mechanical pain was significantly associated with greater average clinical pain severity. Results of this study suggest that enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain.
Similar content being viewed by others
References
Annual update of the HHS poverty guidelines. (2017) Department of Health and Human Services, https://aspe.hhs.gov/2017-poverty-guidelines. Accessed June 21, 2018
Arnow BA, Hunkeler EM, Blasey CM, Lee J, Constantino MJ, Fireman B et al (2006) Comorbid depression, chronic pain, and disability in primary care. Psychosom Med 68(2):262–268. https://doi.org/10.1097/01.psy.0000204851.15499.fc
Bannister K, Dickenson AH (2016) What do monoamines do in pain modulation? Curr Opin Support Palliat Care 10(2):143–148. https://doi.org/10.1097/SPC.0000000000000207
Bulls HW, Freeman EL, Anderson AJ, Robbins MT, Ness TJ, Goodin BR (2015) Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition. J Pain Res 8:311–320. https://doi.org/10.2147/JPR.S84607
Cruz-Almeida Y, Fillingim RB (2014) Can quantitative sensory testing move us closer to mechanism-based pain management? Pain Med 15(1):61–72. https://doi.org/10.1111/pme.12230
Dalakas MC (2001) Peripheral neuropathy and antiretroviral drugs. J Peripher Nerv Syst 6(1):14–20
Dobalian A, Tsao JC, Duncan RP (2004) Pain and the use of outpatient services among persons with HIV: results from a nationally representative survey. Med Care 42(2):129–138. https://doi.org/10.1097/01.mlr.0000108744.45327.d4
Edens JL, Gil KM (1995) Experimental induction of pain: utility in the study of clinical pain. Behav Ther 26:197–216
Ehde DM, Dillworth TM, Turner JA (2014) Cognitive-behavioral therapy for individuals with chronic pain: efficacy, innovations, and directions for research. Am Psychol 69(2):153–166. https://doi.org/10.1037/a0035747
Eide PK (2000) Wind-up and the NMDA receptor complex from a clinical perspective. Eur J Pain 4(1):5–15. https://doi.org/10.1053/eujp.1999.0154
Evans S, Weinberg BA, Spielman L, Fishman B (2003) Assessing negative thoughts in response to pain among people with HIV. Pain 105(1–2):239–245
Gabbai AA, Castelo A, Oliveira AS (2013) HIV peripheral neuropathy. Handb Clin Neurol 115:515–529. https://doi.org/10.1016/B978-0-444-52902-2.00029-1
Geisser ME, Roth RS, Robinson ME (1997) Assessing depression among persons with chronic pain using the Center for Epidemiological Studies-Depression Scale and the Beck depression inventory: a comparative analysis. Clin J Pain 13(2):163–170
Goodin BR, McGuire L, Allshouse M, Stapleton L, Haythornthwaite JA, Burns N, Edwards RR (2009) Associations between catastrophizing and endogenous pain-inhibitory processes: sex differences. J Pain 10(2):180–190. https://doi.org/10.1016/j.jpain.2008.08.012
Goodin BR, Glover TL, Sotolongo A, King CD, Sibille KT, Herbert MS et al (2013) The association of greater dispositional optimism with less endogenous pain facilitation is indirectly transmitted through lower levels of pain catastrophizing. J Pain 14(2):126–135. https://doi.org/10.1016/j.jpain.2012.10.007
Goodin, B. R., Bulls, H. W., Herbert, M. S., Schmidt, J., King, C. D., Glover, T. L., … Fillingim, R. B. (2014). Temporal summation of pain as a prospective predictor of clinical pain severity in adults aged 45 years and older with knee osteoarthritis: ethnic differences. Psychosom Med, 76(4):302–310. doi:https://doi.org/10.1097/PSY.0000000000000058
Goodin BR, Owens MA, Yessick LR, Rainey RL, Okunbor JI, White DM, Merlin JS (2017) Detectable viral load may be associated with increased pain sensitivity in persons living with HIV: preliminary findings. Pain Med 18(12):2289–2295. https://doi.org/10.1093/pm/pnx057
Granovsky Y, Yarnitsky D (2013) Personalized pain medicine: the clinical value of psychophysical assessment of pain modulation profile. Rambam Maimonides Med J 4(4):e0024. https://doi.org/10.5041/RMMJ.10131
Griffith LE, Shannon HS, Wells RP, Walter SD, Cole DC, Cote P, Langlois LE (2012) Individual participant data meta-analysis of mechanical workplace risk factors and low back pain. Am J Public Health 102(2):309–318. https://doi.org/10.2105/AJPH.2011.300343
Griswold GA, Evans S, Spielman L, Fishman B (2005) Coping strategies of HIV patients with peripheral neuropathy. AIDS Care 17(6):711–720. https://doi.org/10.1080/09540120412331336715
Heinricher MM, Tavares I, Leith JL, Lumb BM (2009) Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev 60(1):214–225. https://doi.org/10.1016/j.brainresrev.2008.12.009
Holguin A, O'Connor KA, Biedenkapp J, Campisi J, Wieseler-Frank J, Milligan ED, Watkins LR (2004) HIV-1 gp120 stimulates proinflammatory cytokine-mediated pain facilitation via activation of nitric oxide synthase-I (nNOS). Pain 110(3):517–530. https://doi.org/10.1016/j.pain.2004.02.018
Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Stat 6:65–70
Jensen MP, Karoly P (1992) Self-report scales and procedures for assessing pain in adults. In: Turk DC, Melzack R (eds) Handbook of pain assessment. Guilford Press, New York, pp 135–151
Ji RR, Nackley A, Huh Y, Terrando N, Maixner W (2018) Neuroinflammation and central sensitization in chronic and widespread pain. Anesthesiology 129:343–366. https://doi.org/10.1097/ALN.0000000000002130
Jiao JM, So E, Jebakumar J, George MC, Simpson DM, Robinson-Papp J (2016) Chronic pain disorders in HIV primary care: clinical characteristics and association with healthcare utilization. Pain 157(4):931–937. https://doi.org/10.1097/j.pain.0000000000000462
King CD, Sibille KT, Goodin BR, Cruz-Almeida Y, Glover TL, Bartley E, Fillingim RB (2013) Experimental pain sensitivity differs as a function of clinical pain severity in symptomatic knee osteoarthritis. Osteoarthr Cartil 21(9):1243–1252. https://doi.org/10.1016/j.joca.2013.05.015
Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10(9):895–926. https://doi.org/10.1016/j.jpain.2009.06.012
Le Bars D (2002) The whole body receptive field of dorsal horn multireceptive neurones. Brain Res Brain Res Rev 40(1–3):29–44
Lucey BP, Clifford DB, Creighton J, Edwards RR, McArthur JC, Haythornthwaite J (2011) Relationship of depression and catastrophizing to pain, disability, and medication adherence in patients with HIV-associated sensory neuropathy. AIDS Care 23(8):921–928. https://doi.org/10.1080/09540121.2010.543883
Magerl W, Wilk SH, Treede RD (1998) Secondary hyperalgesia and perceptual wind-up following intradermal injection of capsaicin in humans. Pain 74(2–3):257–268
Martini C, van Velzen M, Drewes A, Aarts L, Dahan A, Niesters M (2015) A randomized controlled trial on the effect of Tapentadol and morphine on conditioned pain modulation in healthy volunteers. PLoS One 10(6):e0128997. https://doi.org/10.1371/journal.pone.0128997
Merlin JS, Cen L, Praestgaard A, Turner M, Obando A, Alpert C, Frank I (2012a) Pain and physical and psychological symptoms in ambulatory HIV patients in the current treatment era. J Pain Symptom Manag 43(3):638–645. https://doi.org/10.1016/j.jpainsymman.2011.04.019
Merlin JS, Westfall AO, Raper JL, Zinski A, Norton WE, Willig JH et al (2012b) Pain, mood, and substance abuse in HIV: implications for clinic visit utilization, antiretroviral therapy adherence, and virologic failure. J Acquir Immune Defic Syndr 61(2):164–170. https://doi.org/10.1097/QAI.0b013e3182662215
Merlin JS, Westfall AO, Chamot E, Overton ET, Willig JH, Ritchie C, Mugavero MJ (2013) Pain is independently associated with impaired physical function in HIV-infected patients. Pain Med 14(12):1985–1993. https://doi.org/10.1111/pme.12255
Merlin JS, Long D, Becker WC, Cachay ER, Christopolous KA, Claborn K, Gross R (2018) The association of chronic pain and long-term opioid therapy with HIV treatment outcomes. J Acquir Immune Defic Syndr 79:77–82. https://doi.org/10.1097/QAI.0000000000001741
Miaskowski C, Penko JM, Guzman D, Mattson JE, Bangsberg DR, Kushel MB (2011) Occurrence and characteristics of chronic pain in a community-based cohort of indigent adults living with HIV infection. J Pain 12(9):1004–1016. https://doi.org/10.1016/j.jpain.2011.04.002
Myers TA (2011) Goodbye listwise deletion: presenting hotdeck imputation as an easy and effective tool for handling missing data. Communication Measures & Methods 5:297–310
Nahman-Averbuch H, Nir RR, Sprecher E, Yarnitsky D (2016) Psychological factors and conditioned pain modulation: a meta-analysis. Clin J Pain 32(6):541–554. https://doi.org/10.1097/AJP.0000000000000296
Natamba BK, Achan J, Arbach A, Oyok TO, Ghosh S, Mehta S, Young SL (2014) Reliability and validity of the center for epidemiologic studies-depression scale in screening for depression among HIV-infected and -uninfected pregnant women attending antenatal services in northern Uganda: a cross-sectional study. BMC Psychiatry 14:303. https://doi.org/10.1186/s12888-014-0303-y
Niesters M, Aarts L, Sarton E, Dahan A (2013) Influence of ketamine and morphine on descending pain modulation in chronic pain patients: a randomized placebo-controlled cross-over proof-of-concept study. Br J Anaesth 110(6):1010–1016. https://doi.org/10.1093/bja/aes578
Nir RR, Yarnitsky D (2015) Conditioned pain modulation. Curr Opin Support Palliat Care 9(2):131–137. https://doi.org/10.1097/SPC.0000000000000126
O'Brien AT, Deitos A, Trinanes Pego Y, Fregni F, Carrillo-de-la-Pena MT (2018) Defective endogenous pain modulation in fibromyalgia: a meta-analysis of temporal summation and conditioned pain modulation paradigms. J Pain. https://doi.org/10.1016/j.jpain.2018.01.010
O'Donnell LA, Agrawal A, Jordan-Sciutto KL, Dichter MA, Lynch DR, Kolson DL (2006) Human immunodeficiency virus (HIV)-induced neurotoxicity: roles for the NMDA receptor subtypes. J Neurosci 26(3):981–990. https://doi.org/10.1523/JNEUROSCI.4617-05.2006
Ohrbach R, Gale EN (1989) Pressure pain thresholds in normal muscles: reliability, measurement effects, and topographic differences. Pain 37(3):257–263
Ossipov MH The perception and endogenous modulation of pain. Scientifica (Cairo) 2012, 2012:561761–561725. https://doi.org/10.6064/2012/561761
Ossipov MH, Dussor GO, Porreca F (2010) Central modulation of pain. J Clin Invest 120(11):3779–3787. https://doi.org/10.1172/JCI43766
Ossipov MH, Morimura K, Porreca F (2014) Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care 8(2):143–151. https://doi.org/10.1097/SPC.0000000000000055
Owens MA, Bulls HW, Trost Z, Terry SC, Gossett EW, Wesson-Sides KM, Goodin BR (2016) An examination of pain catastrophizing and endogenous pain modulatory processes in adults with chronic low Back pain. Pain Med 17(8):1452–1464. https://doi.org/10.1093/pm/pnv074
Parker R, Stein DJ, Jelsma J (2014) Pain in people living with HIV/AIDS: a systematic review. J Int AIDS Soc 17:18719. https://doi.org/10.7448/IAS.17.1.18719
Piche M, Arsenault M, Poitras P, Rainville P, Bouin M (2010) Widespread hypersensitivity is related to altered pain inhibition processes in irritable bowel syndrome. Pain 148(1):49–58. https://doi.org/10.1016/j.pain.2009.10.005
Price DD, Hu JW, Dubner R, Gracely RH (1977) Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses. Pain 3(1):57–68
Quartana PJ, Campbell CM, Edwards RR (2009) Pain catastrophizing: a critical review. Expert Rev Neurother 9(5):745–758. https://doi.org/10.1586/ern.09.34
Radloff LS (1977) A self-report depression scale for research in the general population. Appl Psychol Meas 1(3):385–401
Rhudy JL, Martin SL, Terry EL, France CR, Bartley EJ, DelVentura JL, Kerr KL (2011) Pain catastrophizing is related to temporal summation of pain but not temporal summation of the nociceptive flexion reflex. Pain 152(4):794–801. https://doi.org/10.1016/j.pain.2010.12.041
Ryscavage P, Kelly S, Li JZ, Harrigan PR, Taiwo B (2014) Significance and clinical management of persistent low-level viremia and very-low-level viremia in HIV-1-infected patients. Antimicrob Agents Chemother 58(7):3585–3598. https://doi.org/10.1128/AAC.00076-14
Sarmati L, D'Ettorre G, Parisi SG, Andreoni M (2015) HIV replication at low copy number and its correlation with the HIV reservoir: a clinical perspective. Curr HIV Res 13(3):250–257
Spudich S, Gonzalez-Scarano F (2012) HIV-1-related central nervous system disease: current issues in pathogenesis, diagnosis, and treatment. Cold Spring Harb Perspect Med 2(6):a007120. https://doi.org/10.1101/cshperspect.a007120
Starkweather AR, Heineman A, Storey S, Rubia G, Lyon DE, Greenspan J, Dorsey SG (2016) Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain. Appl Nurs Res 29:237–241
Staud R (2012) Abnormal endogenous pain modulation is a shared characteristic of many chronic pain conditions. Expert Rev Neurother 12(5):577–585. https://doi.org/10.1586/ern.12.41
Staud R (2013) The important role of CNS facilitation and inhibition for chronic pain. Int J Clin Rheumtol 8(6):639–646. https://doi.org/10.2217/ijr.13.57
Staud R, Vierck CJ, Cannon RL, Mauderli AP, Price DD (2001) Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain 91(1–2):165–175
Staud R, Weyl EE, Riley JL 3rd, Fillingim RB (2014) Slow temporal summation of pain for assessment of central pain sensitivity and clinical pain of fibromyalgia patients. PLoS One 9(2):e89086. https://doi.org/10.1371/journal.pone.0089086
Sullivan MJL, Bishop SR, Pivik J (1995) The pain catastrophizing scale: development and validation. Psychol Assess 7(4):524–532
Tan G, Jensen MP, Thornby JI, Shanti BF (2004) Validation of the brief pain inventory for chronic nonmalignant pain. J Pain 5(2):133–137. https://doi.org/10.1016/j.jpain.2003.12.005
Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, … Wang SJ (2015) A classification of chronic pain for ICD-11. Pain 156(6):1003–1007. doi:https://doi.org/10.1097/j.pain.0000000000000160
van Wilgen CP, Vuijk PJ, Kregel J, Voogt L, Meeus M, Descheemaeker F, … Nijs J (2018) Psychological distress and widespread pain contribute to the variance of the central sensitization inventory: a cross-sectional study in patients with chronic pain. Pain Pract, 18(2):239–246. doi:https://doi.org/10.1111/papr.12600
Woolf CJ (2011) Central sensitization: implications for the diagnosis and treatment of pain. Pain 152(3 Suppl):S2–S15. https://doi.org/10.1016/j.pain.2010.09.030
Yarnitsky D (2015) Role of endogenous pain modulation in chronic pain mechanisms and treatment. Pain 156(Suppl 1):S24–S31. https://doi.org/10.1097/01.j.pain.0000460343.46847.58
Yarnitsky D, Arendt-Nielsen L, Bouhassira D, Edwards RR, Fillingim RB, Granot M, Wilder-Smith O (2010) Recommendations on terminology and practice of psychophysical DNIC testing. Eur J Pain 14(4):339. https://doi.org/10.1016/j.ejpain.2010.02.004
Yarnitsky D, Granot M, Granovsky Y (2014) Pain modulation profile and pain therapy: between pro- and antinociception. Pain 155(4):663–665. https://doi.org/10.1016/j.pain.2013.11.005
Yarnitsky D, Bouhassira D, Drewes AM, Fillingim RB, Granot M, Hansson P, Wilder-Smith OH (2015) Recommendations on practice of conditioned pain modulation (CPM) testing. Eur J Pain 19(6):805–806. https://doi.org/10.1002/ejp.605
Yuan SB, Shi Y, Chen J, Zhou X, Li G, Gelman BB, Tang SJ (2014) Gp120 in the pathogenesis of human immunodeficiency virus-associated pain. Ann Neurol 75(6):837–850. https://doi.org/10.1002/ana.24139
Zelman DC, Gore M, Dukes E, Tai KS, Brandenburg N (2005) Validation of a modified version of the brief pain inventory for painful diabetic peripheral neuropathy. J Pain Symptom Manag 29(4):401–410. https://doi.org/10.1016/j.jpainsymman.2004.06.018
Acknowledgements
This research was supported by the Creative and Novel Ideas in HIV Research Program (B.R.G.) through a supplement to the University of Alabama at Birmingham Center for AIDS Research funding (P30AI027767). This funding was made possible by collaborative efforts of the Office of AIDS Research, the National Institute of Allergy and Infectious Diseases, and the International AIDS Society. This research was also supported by the National Institutes of Health K23MH104073 (J.S.M.). None of the authors have any conflicts of interest to report.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Owens, M.A., Parker, R., Rainey, R.L. et al. Enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain. J. Neurovirol. 25, 57–71 (2019). https://doi.org/10.1007/s13365-018-0686-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13365-018-0686-5