Nociceptive Flexion Reflex Threshold in Chronic Pain Patients

Abstract

Background The nociceptive flexion reflex is a physiological, polysynaptic reflex triggered by a nociceptive stimulus activating a withdrawal response. In chronic musculoskeletal-related pain conditions, a decreased nociceptive flexion reflex threshold has been suggested as a possible recognition evidence for central sensitization that may cause alteration of central nervous system processing. Objective The aim of the study was to systematically review reported comparisons of the nociceptive flexion reflex threshold in chronic pain patients and healthy individuals. Methods Electronic databases covering studies published between January 1990 and December 2019 were systematically searched. After application of exclusion criteria, 20 studies including 28 trials were included in this review. For meta-analysis, we used a random-effects model and funnel plot for publication bias. This research was registered at PROSPERO (CRD42019140354). Results Compared with healthy controls, standardized mean differences in nociceptive flexion reflex threshold were significantly lower in the total sample of chronic pain patients. Subgroup analysis indicated a homogenous decreased nociceptive flexion reflex threshold in studies reporting fibromyalgia, chronic pain, and joint pain while heterogeneity existed in other included pain conditions. Conclusions A lower nociceptive flexion reflex threshold in patients experiencing chronic pain conditions may imply hyperexcitability in central nervous system processing. As a preliminary study, the findings would act as a basis for developing a methodology assisting current clinical practices

Modulation of the nociceptive flexion reflex by conservative therapy in patients and healthy people: a systematic review and meta-analysis

“…This may suggest that reduced spinal nociception after conservative interventions is limited to patients in whom enhanced spinal nociception has been demonstrated. 4,23 Furthermore, the observed NFR area inhibition seemed to be the result of the effects of TMS, whereas biofeedback training, tsDCS, and nNVS seemed to contribute little to the significant NFR area inhibition.…”

“…If research in chronic pain patients shows the NFR to be modulated by conservative therapy, we do not know whether this modulation can be attributed to the therapy or by enhanced spinal nociception (measured through decreased NFR thresholds and increased temporal summation of the NFR) that has already been demonstrated in this population. 4,52 Second, it might be clinically relevant to investigate whether the NFR is modifiable by conservative therapy in healthy people. For example, it might be interesting to know whether interventions aiming to promote a healthy lifestyle would be capable of modifying the NFR.…”

“…As the NFR outcome measures may vary between studies because of different methodological procedures and the condition of the study sample (healthy vs disorder), a random-effects meta-analysis with the inverse variance method and the DerSimonian-Laird estimator (for t 2 ) was performed. 9 Although enhanced spinal nociception (ie, lower NFR threshold or larger NFR magnitude) is typically seen in chronic pain populations, 4,52 a previous research report indicated that central sensitization (ie, NFR threshold value below a cutoff value of 27.6 mA) was present in 27.4% of the healthy pain-free control population, 25 which might suggest that also healthy individuals can show signs of central sensitization. This hypothesis is further supported by a recent prospective analysis demonstrating that less efficient endogenous inhibition of spinal nociception predicts future chronic pain risk in healthy pain-free people.…”

Nociceptive Flexion Reflex Threshold is No Suitable Marker for Diagnosing Opioid-Induced Hyperalgesia

“…What implied NFR-T assessment as considerable method for investigating OIH is that decreased NFR-T correlated with hyperexcitability of the central nervous system in patients with chronic pain. 47 Furthermore, multiple studies have reported a decreased threshold in patients with secondary hyperalgesia. 48 , 49 …”

Effects of transcutaneous auricular vagus nerve stimulation at left cymba concha on experimental pain as assessed with the nociceptive withdrawal reflex, and correlation with parasympathetic activity

“…This reflex transmits nociceptive information from sensory receptors to spinal cord interneurons, leading to contraction of flexor muscles on the stimulated side and relaxation of extensors, facilitating escape from the stimulation. The NWR threshold, an objective measure of pain perception, is widely utilized to assess analgesic efficacy and elucidate pain mechanisms (Neziri et al, 2010) and has been associated with chronic pain (Amiri et al, 2021; Biurrun Manresa et al, 2011). stimulating the cervical vagus nerve branch, which also influences the trigeminal nerve, raises uncertainty about whether confined vagus nerve stimulation yields comparable effects.…”