Sleep and Nociceptive Pain

Posted: June 2023

Author: Katie Donnelly, Adv Dip HSc Naturopathy

Sleep and Nociceptive Pain

Herbal support for sleep and nociceptive pain regulation

While pain is known to cause sleep disturbance, a lack of sleep can also increase the perception of pain. This cause-and-effect relationship can perpetuate chronic pain conditions and associated symptoms, including anxiety and depression.¹ Phytomedicine is one of the most used forms of complementary medicine for chronic pain, easing symptoms and supporting healthy sleep regulation.²

Osteoarthritis

Marked by pain, inflammation, and degeneration of cartilage, osteoarthritis (OA) prevalence increases annually, with approximately 500 million people impacted worldwide.³ OA pain is directly associated with sleep disturbance, reduced quality of life and impacted mental wellbeing.^4,5

The active constituents in Salix species (willow), primarily salicin, in combination with flavonoids and polyphenols, have been utilised for pain management for many years. They prevent cyclo-oxygenase (COX) 2 releases of prostaglandins E2, as well as interleukin 1-beta and tumour necrosis factor-alpha (TNF-α). Studies on willow showed improvements in pain compared to placebo, utilising a hydroethanolic preparation.⁶

Salicin also protects against collagen breakdown in OA. Binding of salicin to inositol-requiring enzyme 1 alpha (IRE1α) on the endoplasmic reticulum (ER) alters enzymatic signalling and inhibits the nuclear factor-kappa B (NFKB) pathway. These changes encourage cellular renewal and prevent the apoptosis of chondrocytes.³

Similarly, Zingiber officinale (ginger) interacts with cellular ER signalling to reduce inflammation. Gingerols prevented NFKB activation and subsequently nitic oxide and TNF-α, with a combination of constituents working as antioxidants and reducing reactive oxygen species. Ginger also demonstrated inhibition of COX pathways. Topical applications displayed effective pain relief through the ability to absorb through the epithelium.⁷

Gingerols, shogaols, and zingerone further displayed analgesic actions through binding to transient receptor potential vanilloid subunit 1 (TRPV1) as agonists.⁸ These receptors are upregulated in chronic pain, enhancing pain perception. Shagoal binding to TRPV1 is also behind the warming sensation of ginger, another factor in pain reduction.⁹

Migraine

A close relationship between migraine and impaired sleep has been established, with alterations in sleep regularity and onset correlating with increased experience of pain.¹⁰ This can be related to insufficient or excessive sleep. Conversely, preventative migraine treatment has shown to improve sleep quality, identifying a causality dilemma. As such, a combination of pain and sleep herbal therapy can be beneficial as a treatment protocol.¹¹

Traditionally used for migraine treatment, Tanacetum parthenium (feverfew) showed reduced migraine frequency in recent studies, acting as a prophylactic. The sesquiterpene lactone, parthenolide, is thought to be behind many of this plant’s actions.¹² The inhibition of platelet granule secretion has been demonstrated in vivo, alongside reducing pro-inflammatory cytokines and inducible nitric oxide synthase (INOS.)

However, the interaction with transient receptor potential ankyrin 1 (TRPA1), more recently noted, alters nociceptor sensitivity and prevents calcitonin gene-related peptide (CGRP) release.¹³ Regulation of CGRP is crucial in migraine management, as the powerful dilator is a key factor in transmitting pain signals to the central nervous system.¹⁴

New Zealand native, Dodonaea viscosa (akeake), is another herb traditionally used to ease headaches, as an effective analgesic. A combination of saponins, diterpenoids, and the coumarin fraxetin, contribute to powerful anti-inflammatory activity. Undertaking pain management in the early stages of migraine can aid in reducing the intensity of symptoms, with akeake a suitable option for pre-emptive therapeutic action.¹⁵

Passiflora incarnata (passionflower) can then be utilised as a sedative and nervine supporting herb. Studies on passionflower tea showed positive results in improving sleep in adults, where animal model studies have shown the C-glycoflavonoids vitexin and apigenin as being involved in many sleep-inducing properties, including gamma-aminobutyric acid (GABA) interaction. This herb is also a known anxiolytic and a support in cases of depression^16,17

Fibromyalgia

Marked by chronic and extensive pain of the musculoskeletal system, fibromyalgia is correlated with poor sleep and ongoing fatigue. Anxiety is also closely linked with this condition.

A sacred and traditional analgesic, anxiolytic, and sedative, Piper methysticum (kava) has been used among Pacific Island nations for many years.¹⁸ Kavalactones contribute to many of the actions, with the ability to cross the blood brain barrier. Studies have identified improved GABA type A (GABA_A) activity, comparative to effect of benzodiazepines but not through direct receptor binding.¹⁹ Rather, kava acts as a monoamine oxidase B inhibitor and reduces reuptake of serotonin and dopamine. Improvements in anxiety have then been associated with improvements in sleep, with kavain also recognised as a hypnotic, improving sleep quality through increased delta activity.²⁰

The action of blocking voltage-gated sodium and calcium ion channels contribute to kava’s role as an analgesic, alongside muscle relaxant capabilities.²¹ Anti-inflammatory efficacy has then been shown by kavain, protecting against dangerous levels of lipopolysaccharide (LPS) damage in animal model studies, with flavokavain A and B also preventing INOS and COX-2, prostaglandins, and inflammatory cytokines.²² The combination of symptomatic targeting of pain, anxiety, sleep, and muscle tension contributes to the benefits of kava.

Lavandula angustifolia (lavender), known to induce calm and support sleep, is also a potent anti-inflammatory. A primary terpene, linalool, interacts with cannabinoid receptor 2 and opioid receptors and down regulates hypersensitivity in cases of chronic musculoskeletal pain and inflammation.²³ Further actions include inhibition of LPS pathways and reductions in NFKB, TNF- α, interleukin-beta and interleukin 6.²⁴ Nociceptive pain reduction was noted to be as effective as tramadol and more effective than ibuprofen.²⁵

The nervine tonic, Scutellaria lateriflora (skullcap), has been identified as a co-analgesic though improvements on mood and sleep then improving pain measurement.²⁶ Catechins, bacalein and baicalin also provide relief in cases of nociceptive pain, showing significant action in animal model studies. Potential GABA binding and regulation of intra and extracellular calcium, antioxidant actions, COX regulation, and pro-inflammatory cytokine expression were noted in ethanolic preparations.²⁶

Phytomedicine offers effective treatment for sleep and pain irregularities, helping to support a healthy nervous system and reducing the discomfort of chronic pain.
 

References

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