The Impact of Pain-related Fear on Neural Pathways of Pain Modulation in Chronic Low Back Pain
SOURCE: Pain Rep. 2017 (Apr 11); 2 (3): e601
Michael Lukas Meiera, Philipp Stampfli, Barry Kim Humphreys, Andrea Vrana, Erich Seifritz, Petra Schweinhardt
Department of Chiropractic Medicine,
Interdisciplinary Spinal Research,
University Hospital Balgrist,
INTRODUCTION: Pain-related fear plays a substantial role in chronic low back pain (LBP) by amplifying the experienced disability. Related dysfunctional emotions and cognitions may also affect sensory aspects of pain through a modulatory pathway in which the periaqueductal gray (PAG) and the amygdala play key roles.
OBJECTIVES: We therefore hypothesized a differential amygdala-PAG functional connectivity (FC) in patients with chronic LBP that is modulated by the degree of pain-related fear.
METHODS: We used data of a previously reported fMRI study where 20 chronic LBP patients (7 females, mean age = 39.35) and 20 healthy controls (12 females, mean age = 32.10) were asked to observe video clips showing potentially harmful and neutral activities for the back. Pain-related fear was assessed using the Tampa Scale of kinesiophobia (TSK) and Fear Avoidance Beliefs questionnaires (FABQ). Generalized psychophysiological interactions were used to reveal task-based FC.
RESULTS: Compared to controls, patients exhibited a significant decrease in amygdala-PAG-FC (P = 0.022) during observation of harmful activities, but not of neutral activities. Furthermore, amygdala-PAG-FC correlated negatively with Tampa Scale of kinesiophobia scores in patients (R2 = 0.28, P = 0.01) but not with Fear Avoidance Beliefs questionnaires scores.
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DISCUSSION: Our findings might indicate a maladaptive psychobiological interaction in chronic LBP patients characterized by a disrupted amygdala-PAG-FC that is modulated by the degree of pain-related fear. These results shed new light on brain mechanisms underlying psychological factors that may have pronociceptive effects in chronic LBP.
KEYWORDS: Amygdala; Chronic low back pain; Fear avoidance beliefs; Functional connectivity; Kinesiophobia; PAG; PPI; fMRI
From the FULL TEXT Article:
Chronic low back pain (LBP) accounts for a considerable burden in terms of pain and suffering. [2, 19, 21] Impaired endogenous pain modulation is likely one of the mechanisms contributing to the development and maintenance of chronic pain. [11, 17, 25] The neural circuit underlying emotion and pain modulation comprises 2 key structures that are highly related by sharing functional and structural connections, namely the amygdala and the periaqueductal gray (PAG). [22, 27, 33] The amygdala constitutes an important site for a reciprocal relationship between persistent pain and negative affective states such as fear and anxiety. [4, 10, 23, 24, 31] The PAG is a key region involved in pain modulation and thought to play an important role in the pathogenesis of chronic pain. [5, 14, 33] In support, it has been shown that the resting-state functional connectivity (FC) of the PAG is disrupted in chronic LBP.  However, evidence about modulating factors of amygdala-PAG-FC in chronic LBP is sparse. One potential factor might be pain-related fear. Pain-related fear partly predicts LBP chronification, probably via a vicious circle of cognitive dysfunctions that may ultimately lead to physical deconditioning of the musculoskeletal system. [1, 12, 29, 32] Based on the knowledge that cognitions modulate not only emotional functioning but also sensory aspects of pain perception through endogenous pain modulatory mechanisms,  we hypothesized that pain-related fear modulates the neural crosstalk between the amygdala and the PAG. Therefore, we used an existing data set to specifically test amygdala-PAG-FC and its relationship with the individual degree of pain-related fear in chronic LBP patients and asymptotic controls.