REVIEW ARTICLE Central Sensitization and Altered Central Pain Processing in Chronic Low Back Pain Fact or Myth? Nathalie A. Roussel, PhD, Msc, PT,*w Jo Nijs, PhD, Msc, PT,w y Mira Meeus, PhD, PT,w z z z Veit Mylius, PhD, MD,8z Ce´cile Fayt, PhD, MD,# and Rob Oostendorp, PhD, MPT, PT** (Clin J Pain 2013;29:625–638) Objective: The purpose of this narrative review is to analyze the available literature concerning central sensitization and altered central pain processing in patients with chronic low back pain (LBP). ow back pain (LBP) is one of the most common Methods: Literature was screened using several electronic search Lmusculoskeletal disorders, affecting 70% to 85% of all databases. Additional literature was obtained by reference tracking adults at some point in their life.1 The course of LBP is and expert consultation. Studies evaluating central pain processing characterized by a recurring pattern of reports.2 A sys- in conservatively treated patients with chronic LBP were included. tematic review revealed that 42% to 75% of patients still experience LBP after 12 months,3 accounting for major Results: Results of studies examining the responsiveness to various 1 stimuli in patients with chronic LBP are conflicting. Some studies in expenses in health care and disability systems. Chronic patients with chronic LBP have demonstrated exaggerated pain LBP therefore remains a public health burden for the responses after sensory stimulationoflocationsoutsidethepainful industrialized world. region, while other studies report no differences between patients and Despite the high incidence and prevalence of LBP,4 little healthy subjects. Studies examining the integrity of the endogenous is known about the precise causes. Degenerative processes pain inhibitory systems report unaltered activity of this descending and/or impairments in body structures of the lumbar verte- inhibitory system. In contrast, studies analyzing brain structure and bral column and musculoskeletal structures related to function in relation to (experimentally induced) pain provide prelim- movement are regularly seen on imaging results, but these inary evidence for altered central nociceptive processing in patients impairments do not explain the symptoms in all patients with with chronic LBP. Finally, also psychosocial characteristics, such as 5 inappropriate beliefs about pain,paincatastrophizing,and/or LBP, as they are also observed in healthy controls (HC). The depression may contribute to the mechanisms of central sensitization. association between symptoms and imaging results has been consistently weak in patients with LBP.6 As a precise path- Conclusions: It tempting to speculate that ongoing nociception is oanatomic diagnosis cannot be given in approximately 85% associated with cortical and subcortical reorganization and may of the patients with LBP,4 LBP in these patients is therefore play an important role in the process of the chronification of LBP. Future prospective research should explore to what extent these considered nonspecific LBP. The observation that only 25% changes are reversible and if this reversibility is associated with of the variance of back pain intensity can be explained by the 7 improved functioning of patients. joint contribution of pathology and psychosocial factors, confirms the need of further exploration of contributing and Key Words: central nervous system, hyperexcitability, chronic pain, underlying mechanisms. low back pain, hyperalgesia, neuroplasticity Pain in some other chronic conditions, such as fibro- myalgia (FM), appears to result from abnormal central pain processing, rather than from damage and injury to anatomic Received for publication July 4, 2011; revised July 20, 2012; body structures.8 For example, prolonged or strong activity in accepted August 16, 2012. the dorsal horn neurons may lead to increased neuronal From the *Faculty of Medicine and Health Sciences, University of responsiveness and central sensitization (CS).9–11 This central Antwerp, Wilrijk; wDepartment of Health Care Sciences, Division of Musculoskeletal Physiotherapy (Chropiver), Artesis University hyperexcitability could account for mechanical hyperalgesia, College, Antwerp; Department of Human Physiology (Chropiver), allodynia, and/or referred pain which are frequently observed Faculty of Physicalz Education & Physiotherapy, Vrije Universiteit in chronic pain syndromes.11–15 Brussel (VUB); yDepartment of Physical Medicine and Physi- otherapy, University Hospital Brussels (UZB); #Haute Ecole Le´ o- As sensitization has been defined as an increased nard de Vinci, Institut d’Enseignement Supe´ rieur Parnasse—Deux response to stimulation, this process may occur from Alice, Bruxelles, Belgium; 8Department of Neurology, Philipps nociceptors in peripheral tissues to brain areas responding University of Marburg, Marburg, Germany; zService de to nociceptive inputs. Although the exact mechanisms Physiologie—Explorations Fonctionnelles, Hoˆ pital Henri-Mondor, causing CS remain to be established, several contributing AP-HP, Universite´ Paris 12, Paris, France; and **Scientific Insti- 11,16,17 tute for Quality of Healthcare, Radboud University Nijmegen mechanisms have been identified. “Wind-up” or Medical Centre, Nijmegen-Midden, the Netherlands. temporal summation refers to a spinal mechanism in which The authors declare no conflict of interest. N.A.R. is financially sup- repetitive noxious stimulation results in a slow temporal ported by a postdoctoral grant supplied by the Department of 18 Health Care Sciences, Artesis University College Antwerp, Ant- summation that is experienced as increased pain. While werp, Belgium (G 806). M.M. is a postdoctoral research fellow of wind-up leads to facilitation of ascending pain mechanisms, the Faculty of Physical Education and Physiotherapy, Vrije Uni- alterations of the descending inhibitory pathways, arising versiteit Brussel (VUB), Brussels, Belgium. from the periaqueductal gray matter and the rostral ventral Reprints: Nathalie A. Roussel, PhD, MSc, PT, Faculty of Medicine 19–21 and Health Sciences, University of Antwerp, Universiteitsplein 1, medulla in the brainstem were also described. The Wilrijk 2610, Belgium (e-mail: [email protected]). function attributed to these descending inhibitory pathways Copyright r 2013 by Lippincott Williams & Wilkins is to “focus” the excitation of the dorsal horn neurons, to | Clin J Pain Volume 29, Number 7, July 2013 www.clinicalpain.com 625 Roussel et al Clin J Pain Volume 29, Number 7, July 2013 generate an urgent, localized, and rapid nociceptive signal pain syndrome, FM, and whiplash-associated disorders, as to biologically relevant stimuli, thereby suppressing sur- increased responsiveness to a variety of somatosensory rounding extraneous neuronal activity.22,23 Disruption of stimuli represents a major characteristic of CS. Hyper- Z1 elements of the inhibitory system can result in the algesia is expressed as a lowered pain threshold because of equivalent of CS.23 sensitization of nociceptive afferents or an increased rate of Finally, besides descending inhibitory pathways, facili- growth of pain intensity as a function of graded nociceptive tatory pathways originating from the brainstem have been stimulation.30 In patients with LBP, lower thresholds may identified. Forebrain centers are capable of exerting powerful be observed in areas innervated by spinal segments adjacent influences on various nuclei of the brainstem,24 including the to the spinal segments of the primary source of nociception. nuclei identified as the origin of the descending facilitatory These findings will be considered as segmental CS.31 In case pathway.23 The activity in descending pathways is not con- pain referral and numerous areas of hyperalgesia in sites stant but can be modulated, for example by the level of outside and remote to the symptomatic site are observed, vigilance, attention, expectation, and stress.25 It has been together with an extrasegmental general decrease in pain recognized that forebrain products such as cognitions, emo- thresholds, the term widespread or extrasegmental CS will tions, attention, motivation, and/or stress as personal factors be used.31 Seventeen studies analyzing sensitivity to various may influence the clinical pain experience.23 The term cog- sensory stimuli in patients with chronic LBP were found. nitive-emotional sensitization has been used to designate this Details of the included studies are found in Table 1. In the facilitatory influence.26 In HC, functional imaging studies last column, it is mentioned whether the results of these revealed that psychosocial and cognitive factors such as pain studies are favouring (CS +) or rejecting (CS ) the catastrophizing and expectation were related to neural hypothesis of CS in chronic LBP. À processing of nociceptive stimuli.27,28 Therefore, studies analyzing cerebral processing in Evidence for Segmental or Widespread relation to experimental induced pain in patients with chronic pain are of particular interest. Outstanding efforts Hyperalgesia? have been made during the last decades to unravel brain Mechanical Pressure and/or Electrical Stimulation processing of pain and decode underlying neuronal mech- Four studies reported hyperalgesia to pressure to sites anisms using functional imaging studies.29 Brain-imaging unrelated to the lumbopelvic region in patients with chronic studies may offer both a functional and structural non- LBP, indicating generalized or widespread hyperalgesia at invasive approach to contribute