# Whole-Body Cryostimulation in Fibromyalgiaia: A Scoping Review
## 4 Discussion
### Clinical Effects of WBC in FM  
Pain perception involves interconnected physiological and psychological mechanisms that include anatomical, physiological, cognitive, and affective components of pain [70]. There are two neural pathways that regulate pain signals: ascending pathways that transmit sensory signals through peripheral nerves, including nociceptive signals, to the spine and brain for processing; and descending pathways that send modulatory (excitatory and/or inhibitory) signals from the brain to the periphery, regulating ascending nociceptive signals that reach the brain [71]. These physical and noxious chemical signals are detected by nociceptors, specialized receptors in peripheral nerves activated by physical stimuli (i.e., changes in temperature, pressure, and impact). Many neurotransmitters and neuro-chemicals are involved in the transmission of pain signals such as norepinephrine and serotonin [72]. In FM, these two neural pathways operate abnormally causing an increased activity in the pain matrix which results in central amplification of pain signals, a phenomenon named central sensitization [73]. Several studies of FM-related pain and hyperalgesia have demonstrated the involvement of spinal mechanisms and an enhanced response to somatic and cutaneous stimuli throughout the brain's pain matrix, allodynia and hyperalgesia. In most cases, patients become hypersensitive to pain. The constant hypervigilance to pain can also be associated with psychological problems [74]. Most of the studies included in this review (7 out of 10) hypothesized that WBC should alleviate pain and/or inflammatory processes in FM patients, with the aim of improving health-related quality of life. These studies tested the therapeutic efficacy of WBC and its practicability for clinical routine in FM, also comparing it to other therapies (warm therapy or steam therapy) or treatments (antioxidants and analgesic agents). All studies reported an analgesic effect of WBC with significant reduction in pain level, but had different settings. [PERSON] et al. carried out two studies on the efficacy and safety of WBC in FM patients. The first report showed the superiority of WBC compared to antioxidants and analgesic agents, in terms of pain and fatigue reduction [34]. In the second study, patients performed aerobic exercise (cycle ergometer or treadmill) for 30 min immediately after WBC [33]. Physical activity, which is also used to treat FM, may have masked these results by opposing its induced vasodilation to WBC-induced vasoconstriction. In the cross-over trial of [PERSON] et al., the individuals' VAS and FIQ scores did not return to baseline after the first treatment with WBC due to too short washout periods, so that only results of the first sequence could be reported [40]. [PERSON] et al. reported that WBC significantly improved health-reported quality of life, evaluated through the changes in the Medical Outcome Study Short Form-36 (10 sessions over 8 days) [35]. However, the sample size was limited, as only 11 patients underwent WBC and the control group protocol was not described in detail. This was the same for the study of [PERSON] et al. that described a decreased pain intensity and a short-term pain relief of about 1.5 hafter cold application. No control group receiving a regular rehabilitation program could be compared to a group additionally treated with WBC [36]. Therefore, the reduction in pain could probably be due not only to the analgesic effect of the WBC, but also to the effect of the applications carried out in parallel. However, they described some adjustment time before reaching maximum pain relief, in their case after about two weeks (half of the treatment). Interestingly, most patients rated the effect of WBC as not very effective in the context of the overall treatment, perhaps also due to the session conditions (temperature \(-105\)\({}^{\circ}\)C and 2-3 patients in the chamber). [PERSON] et al.