Analgesic efficacy of sleep-promoting pharmacotherapy in patients with chronic pain: a systematic review and meta-analysis

Abstract

Dysregulation of sleep heightens pain sensitivity and may contribute to pain chronification. Interventions which consolidate and lengthen sleep have the potential to improve pain control. The main objective of this systematic review was to examine the effects of sleep-promoting pharmacotherapy on pain intensity in patients with chronic pain. Multiple electronic databases were searched from inception to January 2022 to identify relevant randomized controlled trials (RCTs). Two independent reviewers screened titles, abstracts, and full-text articles; extracted data; and assessed risk of bias for each included study. The GRADE approach was used to determine the strength of evidence. The search identified 624 articles. After full-text screening, 10 RCTs (n 5 574 randomized participants) involving 3 pharmacologic interventions (melatonin, zopiclone, and eszopiclone) and 7 different chronic pain populations were included. Minimum clinically significant pain reduction $30% was reported in 4 studies. There is low-quality evidence (downgraded due to inconsistency and imprecision) that 2 to 8 weeks treatment with a sleep-promoting medication alone or in combination with an analgesic (6 trials, n 5 397) decreases pain intensity compared with placebo or the same analgesic treatment alone (SMD 20.58 [95% confidence interval 21.00, 20.17], P 5 0.006). Analyses of associations between changes in sleep and pain outcomes were only provided in 2 articles, with inconsistent findings. Notably, pain-relieving effects were most consistent in melatonin trials. Only 3 studies implemented polysomnography to obtain objective sleep measures. Low-quality evidence indicates that pharmacologic sleep promotion may decrease pain intensity in chronic pain populations. More research is needed to fully understand the influence of sleep-targeting interventions on pain control.

Psychosocial characteristics of the general population who habitually use hypnotics: Results from a national survey on drug use among the Japanese

“…Previous studies have suggested an interrelationship between sleep disturbance and chronic pain. 28 , 29 , 31 Sleep disturbances can lead to detrimental psychological and behavioral effects, such as increased depressive and anxiety symptoms, which exacerbate pain. Conversely, increased pain stimulates the sympathetic nervous system and increases the inflammatory response, causing sleep disturbances.…”

“…Some cases have been reported in which insomnia was resolved through cognitive behavioral therapy and chronic pain control in collaboration with these professionals. 29 , 30 , 31 , 46 , 47 …”

“…Previous studies have not provided sufficient information on the patients' backgrounds. In particular, little is known about the status of consumption of other substances by HUs, despite the anticipated association between the characteristics of HUs and insomnia patients because of the presence of psychiatric disorders, 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 chronic pain, 22 , 28 , 29 , 30 , 31 heavy drinking, 1 , 32 smoking, 1 , 33 , 34 , 35 and use of controlled drugs, 32 such as cannabis, cocaine, and opiates, which have been reported as factors that can cause insomnia symptoms. Understanding the psychosocial characteristics of the general population who habitually consume hypnotics could be helpful in policymaking regarding the appropriate use of hypnotics.…”

Changes in Melatonin Concentration in a Clinical Observation Study under the Influence of Low-Frequency Magnetic Fields (Magnetic Stimulation in Men with Low Back Pain)—Results of Changes in an Eight-Point Circadian Profile

“…Evidence of low quality (downgraded due to imprecision) presented by Andersson et al [29] suggests that 4 to 8 weeks of melatonin treatment reduces pain intensity compared with a placebo. The analgesic effect is confirmed in the work of Ahmad et al [6].…”

Insomnia among patients with chronic pain: A retrospective study

“…Chronic pain and insomnia share a close relationship, mutually influencing each other, with numerous reports exploring this connection. [7][8][9][10][11][12] Insomnia affects 10% to 15% of the general population, [11] and research indicates that clinical insomnia is prevalent in over half of the patients with chronic pain, surpassing general population rates. [8] Many individuals with chronic pain struggle with falling asleep or experience sleep disruptions due to pain and insomnia.…”