Alterations in pronociceptive and antinociceptive mechanisms in patients with low back pain: a systematic review with meta-analysis

Abstract

Altered pro-nociceptive and anti-nociceptive mechanisms are often implicated in painful conditions and have been increasingly studied over the past decade. For some painful conditions alterations are well-established, but in low back pain (LBP) populations there remains considerable debate whether these mechanisms are altered. The present systematic review aimed to address this issue by identifying studies assessing Conditioned Pain Modulation (CPM) and/or Temporal Summation of Pain (TSP) in LBP patients, comparing to either a healthy control group or using a method with reference data available. Qualitative synthesis and quantitative meta-analysis of group differences were performed. For CPM and TSP, 20 and 29 original articles were eligible, with data for metaanalysis obtainable from 18 (1500 patients, 505 controls) and 27 (1507 patients, 1127 controls) studies, respectively. Most studies were of poor-to-fair quality with significant heterogeneity in study size, population, assessment methodology and outcome. Nonetheless, CPM was impaired in LBP patients compared to controls (standardized mean difference =-0.44 [-0.64,-0.23], P<0.001), and the magnitude of this impairment was related to pain chronicity (acute/recurrent versus chronic, P=0.003), duration (R=-0.62, P=0.006) and severity (R=-0.54, P=0.02). TSP was facilitated in LBP patients compared to controls (standardized mean difference = 0.50 [0.29, 0.72], P<0.001), and the magnitude of this facilitation was weakly related to pain severity (R=0.41, P=0.04) and appeared to be influenced by test modality (P<0.001). Impaired CPM and facilitated TSP was present in LBP patients compared to controls, though the magnitude of differences was small which may direct future research on the clinical utility.

Exercise-induced hypoalgesia after acute and regular exercise: experimental and clinical manifestations and possible mechanisms in individuals with and without pain

“… 24 Also, Fingleton et al 40 observed reduced pressure pain thresholds (hyperalgesia) after both aerobic and isometric exercises in individuals with knee osteoarthritis who demonstrated an impaired CPM response. By contrast, pain thresholds increased in knee osteoarthritis individuals with a normal CPM response suggesting that patients with impaired CPM, which is also a common finding in individuals with chronic pain, 114 , 121 may have less acute hypoalgesic effect from exercise.…”

“…Individuals with facilitated central pain mechanisms, which are commonly observed in several chronic musculoskeletal pain conditions, 121 often report reduced hypoalgesia after exercise. Vaegter et al 197 observed reduced EIH after submaximal isometric exercise and after bicycling exercise in chronic pain patients with high widespread pain sensitivity compared with patients with low pain sensitivity.…”

Tapentadol treatment results in long-term pain relief in patients with chronic low back pain and associates with reduced segmental sensitization

“…Conditioned pain modulation, which is considered a surrogate marker for central pain inhibition, has been extensively studied in many chronic pain syndromes including CLBP. 25 , 26 , 39 A recent meta-analysis evaluating CPM in patients with CLBP demonstrated reduced CPM responses in patients compared with controls. 26 This agrees with the results of this study where the majority of patients with CLBP (87%) showed aberrant CPM responses.…”

“… 1 , 31 , 39 Both a loss of pain inhibition and an increase in pain facilitation have been observed in patients with CLBP. 1 , 25 , 26 However, up to now, we remain uninformed on the association between the endogenous pain system and treatment efficacy in CLBP.…”

Spatial summation of pain increases logarithmically

“…Nevertheless, previous attempts failed to show differences in SSp response profiles between healthy controls and chronic pain patients [16,19,47,49], which raised the question about the mechanism of SSp. Interestingly, previous studies in which other paradigms, also testing pain modulation, such as temporal summation [34], offset analgesia [51] or DNIC, showed distinct differences between chronic patients compared to healthy controls.…”