Abstract
This paper will address how to address pain and inflammation with herbal medicine within a clinical setting from a primarily systems vs. symptoms-based approach. Major mechanisms of action of key herbs will be explored while providing the clinician with a deeper knowledge of a plant’s tissue specify & secondary actions, and thus ability to better individualize treatment protocols, taking a more holistic approach to the management of pain, inflammation and connective tissue healing. Herbal approaches to the resolution of pain & inflammation through the modulation (vs. inhibition) of inflammatory pathways demonstrates a supportive (as opposed to suppressive) therapeutic intervention where the resolution of inflammation can be achieved whilst connective tissue function is both nourished and restored.
Clinical Challenges in Managing Pain & Inflammation
Pain is a complex, initially protective and adaptive response manifesting as a sensory, emotional, and cognitive phenomenon that can frequently out-live its usefulness and impede the body’s ability to function. It is universal to the human experience, and though it can vary greatly in subjective intensity and duration it is inextricable from the inflammatory process as all pain will involve an inflammatory component.[i] Chronic inflammation results in pain and destruction of bone and cartilage that can lead to severe disability and in which systemic changes occur that can even result in the shortening of life.[ii] There are many different types of pain (see Table 1), and such pain pathways involve intricate connections between neurological networks, pain-sensing systems and other neuroendocrine networks.[iii] According to the National Institute of Health, pain is the leading cause of disability and affects more Americans than diabetes, heart disease, and cancer combined. [iv] According to the American Academy of Pain Management the most common types include arthritis, lower back, bone/joint pain, headaches, muscle pain and fibromyalgia.
Most conventional approaches to these conditions focus solely on the symptomatic reduction of pain and/or inflammation as opposed to addressing the underlying causes, contributing factors, or systems imbalances contributing to the patient’s dis-ease. Although alleviation of pain through the use of conventional analgesics & anti-inflammatories can be useful in some cases, our deepening understanding of the processes involved in the resolution of inflammation reveals that targeting singular physiological pathways (i.e. inhibition of pain pathways) is not always in the best interest of the patient, and can in fact in some cases impede the healing process, leading to chronic inflammation while carrying concerns with regards to addiction, dependence, as well as other serious and/or uncomfortable side effects. Moreover, taking this type of symptomatic approach ignores the many potential contributing mechanisms to pain & inflammation (see Table 2).
The transition from acute to chronic pain occurs in discrete pathophysiological and histopathological steps. Under normal conditions, painful stimuli diminish as tissue healing progresses, however persistent or intense pain activates secondary mechanisms that can diminish normal functioning and lead to chronic pain. This transformation of acute to chronic pain include processes involving prostaglandins, endocannabinoids, ion-specific channels to name a few. [v] Chronic pain is more than a symptom, but an illness unto itself with its own set of comorbidities that has been increasing in prevalence and is considered to be the most underestimated health care problem impacting quality of life. [vi]
Supporting the Resolution of Inflammation
Inflammation is a healthy, normal defensive response to injury or irritation involving a complex cascade of immune response signaling and cytokines which are a necessary stage of resolution and wound healing. However when the resolution process is uncontrolled, chronic inflammation can act as the primary cause of a vast continuum of disorders with a variety of presentations, including chronic disease and even cancer.[vii] [viii] Additionally, inflammatory responses in the peripheral and central nervous systems play key roles in the development and persistence of many pathological pain states, as messenger molecules released from inflamed areas can lead to the inappropriate activation of a pain response. Our goal therefore should be to support and improve the control of these complex biological processes whenever possible, and this may be considered difficult if not impossible to accomplish through the use of single targeted therapeutic mechanisms.
Inflammation involves the sequential activation of signaling pathways leading to the production of both pro- and anti-inflammatory mediators. The pro-inflammatory signaling pathways and cellular mechanisms that initiate the inflammatory response have become well characterized, however those mediators and mechanisms that switch off inflammation are only more recently coming to light. Current data indicate that the resolution of inflammation is an active process controlled by endogenous mediators that suppress pro-inflammatory gene expression and cell trafficking, as well as induce inflammatory-cell apoptosis and phagocytosis, which are crucial determinants of successful resolution.[ix] For example, it has been demonstrated that the transcription factor NF-κB, whose activation was primarily thought to have a central role in the induction of pro-inflammatory gene expression, is associated with the expression of anti-inflammatory genes and the induction of apoptosis, and inhibition of NF-κB during the resolution of inflammation protracts the inflammatory response and prevents apoptosis, suggesting that NF-κB actually has an anti-inflammatory role in the regulation of inflammatory resolution, thus its complete inhibition may in fact be detrimental in vivo.[x]
Table 1: Types of Pain
- Mechanical damage/trauma (e.g. acute/nociceptive)
- Joint (capsule stretch)
- Ligaments (sprain, tear)
- Muscle (strain, tear, spasm)
- Tendon (strain, tear)
- Radicular (impingement)
- Acute vs. Chronic Inflammatory (”itis” vs. degeneration & Repetitive trauma/injury “osis”)
- Systemic disease process (e.g. auto-immune, metabolic)
- Vascular (claudication)
Table 2: Potential Contributing Mechanisms to Pain and Inflammation
- Autoimmunity
- Food Allergy & Sensitivity
- Poor Gut health (chronic infections, alterations in microbiome)
- Hormonal imbalance
- Neuroendocrine disruption
- Poor Diet and Hydration (Nutrient depletion)
- Posture/Ergonomics
- Stress/Depression/Anxiety
- Sleep Disturbance
- Lifestyle Factors
- Socioeconomic Factors
- Social Relationships & Support
- Xenobiotic burden
The Resolving Pain & Inflammation with Herbal Medicine
As we are learning, the resolution phase of inflammation is just as actively orchestrated as its induction and inhibition.[i] Thus the treatment of pain and inflammation should not be restricted to the use of inhibitors of the acute cascade, but broadened to take account of the enormous therapeutic potential of inducers and/or modulators of the resolution phase of inflammation. This recent emphasis toward resolution is crucial towards our understanding of how immune-mediated inflammatory responses are actually terminated. Inflammatory responses, like all biological cascades, are shaped by a delicate balance between positive and negative feedback loops, and resolution involves reprogramming of cellular functions while simultaneously preparing tissue for regeneration after the cause of inflammation is removed.[ii] This is where the use of herbal medicine can be incredibly helpful, acting at multiple phases of healing and within various pro-resolution pathways as modulators, not suppressors, of the pro-resolving inflammatory process.
Many herbal medicines have the ability to act as mediators or modulators of inflammation while simultaneously reducing pain and aiding in tissue repair and regeneration. These herbs are often referred to collectively as Anti-rheumatics, which provides an umbrella term for many herbs that used traditionally to treat pain and inflammation of the muscles & joints. Even when administered at the onset of an acute inflammatory response they will allow the initiation phase to occur while often aiding in both the removal of tissue waste products and providing nourishment in the way of key macro/micro & phytonutrients. Relative to conventional drugs the majority of herbs generally carry a low risk of adverse effects, and can often be safely combined with existing pain treatments, and when combined together will often demonstrate synergetic effects on multiple pathways involved in the the propagation of pain & inflammatory signaling, as well as systems and tissue specific wound-healing (vulnerary) effects.
Herbal medicines will vary in regards to the quality and availability of clinical evidence, and certain plants will have much more known regarding their particular phytonutrient profile and mechanism of action. For example, “curcumin and inflammation” yields over 100,000 scholarly articles, while “California poppy & pain” yields a small fraction of that amount. When less is known regarding a particular herbal medicine the importance of drawing on traditional and historical uses of plants is encouraged, especially in relation to providing ideal dosing strategies and identifying obvious safety and/or toxicity concern. There are several plant constituents however where much more is known regarding their effects on pain & inflammation, for example the alkaloids found within the Papaveraceae family which act on our endogenous opioid system have been recognized as some of our most potent inhibitors of pain (both mental & emotional) for decades [iii], endogenous cannabinoids in the cerebral cortex which also modulate pain sensation and responses [iv], and the salicylates which appear to work primarily by interfering with production of prostaglandin synthesis & bradykinin during tissue damage and inflammation.[v] As clinicians it can be helpful to look to herbs that operate within these pathways. Table 4 provides an overview of some potential target mechanisms when addressing pain and inflammation, while table 5 provides an overview of some of the most commonly recognized mechanisms of action, active constituents and herbal examples.
Table 3. Comparative Knowledge of Herbal Medicines
- Traditional & Historical uses
- Tissue & Organ system Affinity
- Known Secondary metabolite (constituent) profile, activity & bioavailability.
- Quality & availability of clinical evidence.
- Ideal method of herbal pharmacy, route of administration & dosing strategy.
- Adverse effects, toxicity concerns and/or drug interactions.
Table 4. Target Mechanisms for Management of Pain and Inflammation
- COX/LOX – Cytokines (bradykinin)
- Opioid receptor system
- Endocannabinoid system
- Inhibitory Neurotransmitter Agonists (i.e. GABA, serotonin)
- Endocrine – HPA axis (Cortisol agonist)
- Immune (T1/T2 Modulation, histamine)
- Excitatory Neurotransmitter Antagonist (i.e. Glutamate)
- Topical Applications (i.e. substance P)
Table 5. Plant Mechanisms in Management of Pain and Inflammationxvi
Mechanism | Constituent(s) | Herbal Examples |
Opioid | Isoquinoline Alkaloids |
Corydalis spp. (Golden Smoke/ Yanhusuo) Eschscholzia californica (California poppy) |
Prostaglandin | Salicylates Curcumin Resin |
Salix alba (Willow bark) Tanacetum parthenium (Feverfew) Curcuma longa (Turmeric) Boswellia serrata (Frankincense) Commiphora molmol (Myrrh) |
Neurokinins (Substance P) | Capsaicin | Capscium spp. (Cayenne) |
Cannabinoid | Phytocannabinoids | Cannabis spp. (Cannabis) |
Ion Channels | Resin (Kava lactones) | Piper methysticum (Kava Kava) |
Endocrine (HPA axis) | Steroidal & Triterpenoid Saponins | Withania somnifera (Ashwagandha) Glycyrrhiza glabra (Licorice) |
1) First Line: Herbal Anti-inflammatories (Inflammatory Modulators) & Analgesics
It is increasingly inaccurate to refer to herbs as anti-inflammatories at all, as they are in fact modulators of such physiological processes in a way that suits normal balance between inflammatory & anti-inflammatory mediators by maintaining a balance between cytokines and acting as antioxidants, immunomodulators, or any form of action that helps to inflammation process and normalize the immune response.[i] Nonetheless, what are known as anti-inflammatory botanicals will also often have direct analgesic properties and might be considered in patients with inflammation-related pain. A number of botanical medicines have proven effective for relieving different forms of pain though a variety of physiologic mechanisms (see table 5) of which some have been well delineated and others are less well understood. Analgesic effects of herbs are typically slower acting than conventional ones but longer lasting, and will exert anti-inflammatory effects in a “concentration-dependent” or “dose-dependent” manner.[ii] It is also worth noting that many of these herbs are known to exert such effects when applied either topically or taken internally.
Herbal Example | Key Clinical Indications | Safety Concerns/Contraindications |
Salix alba (Willow bark) |
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Boswellia serrata (Frankincense) |
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Commiphora molmol (Myrrh) |
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Curcuma longa (Turmeric) |
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Zingiber officinalis (Ginger) |
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2) Addressing Contributing Causes:
a) Stress, Sleep & Mood Disorders
Studies on pain–depression comorbidity have shown that: (a) pain is as strongly associated with anxiety and depressive disorders, and (b) certain psychological symptoms (low energy, disturbed sleep, worry) are prominent among pain patients.[i] It is also a common clinical experience that anxiety about pain can exacerbate the pain sensation. Chronically painful conditions are frequently associated with sleep disturbances, and it is becoming increasingly recognized that disturbances of sleep can in fact cause or modulate both acute and chronic pain.[ii] Interestingly, most of the herbal medicines used for improving sleep, stress and mood disorders (e.g. depression & anxiety) also have analgesic, antispasmodic, and anti-inflammatory activity. The mechanism of action of some of these herbs has yet to be fully elucidated, so most of our information is based on centuries of clinical experience. For safety, heavy machinery should not be operated while taking herbs in this category that have sedative effects, and clinicians should be aware that combining these herbs alongside other sedatives will likely have additive effects.
Table 7. Nervine Relaxants/Sedatives and Antispasmodics
Botanical | Key Clinical Indications | Safety Concerns/Contraindications |
Corydalis spp. (Corydalis) |
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Eschscholzia californica (California Poppy) |
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Piscidia piscipula (Jamaican Dogwood) |
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Passiflora incarnata (Passionflower) |
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Piper methysticum (Kava Kava) |
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Hypericum perforatum (St. John’s Wort) |
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Viburnum opulus (Cramp bark) |
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b) HPA Axis Dysregulation
Adrenal hormones (i.e. norepinephrine (NE) & cortisol) are also integrally involved in the resolution of inflammation. The stress hormones produced by the HPA axis have a direct effect on the phases of inflammation and create downstream metabolic effects including insulin and cortisol resistance. Resolution of inflammation can only take place when NE is equal to the level of cortisol (plus insulin), and the stop signal for inflammation requires a low level of NE along with normalized cortisol sensitivity.[i] Adaptogenic herbs can work on both by aiding in the resolution of the inflammatory process by modulating cortisol activity via the HPA access, as well as key mediators of inflammation. Sustained elevated cortisol levels can inhibit innate immunity & potentially lead to glucocorticoid receptor resistance, which disrupts the body’s ability to naturally resolve inflammation.[ii] It’s important to note that adaptogens do not inhibit the stress response, but improves stress response (often via hormetic effects), normalizing stress-induced elevated levels of cortisol and other extra/intracellular mediators of stress response (e.g. elevated NO, SAPK via upregulated expression of NPY and heat shock proteins).[iii]
Table 8. Adaptogens
Botanical | Key Clinical Indications | Safety Concerns/Contraindications |
Withania somnifera (Ashwagandha) |
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Glycyrrhiza glabra (Licorice) |
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Panax ginseng (Asian ginseng) |
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3) Healing & Supporting Tissue Damage
Resolution of inflammation must involve tissue repair & regeneration.[i] Once pain and inflammation have been adequately controlled herbs can be employed to help speed wound healing, collagen formation, angiogenesis, and increase antioxidant levels within the wound especially in early stages of tissue repair. Promoting the repair of damaged connective tissue shortens the wound healing process and in some cases may suppress the formation of scar tissue.
The herbs which are used to this end are often highly nutritional and can support circulation & improve the health and integrity of the microvasculature through phytonutrients such as bioflavonoids, saponins and allantoin. In this way many act as “alteratives” (aka. tissue detoxifiers) that can improve the removal of metabolic waste products through the lymphatic systemic and this reduce tissue swelling and edema.
Table 9. Connective Tissue Tonics and Circulatory Stimulants
Botanical | Key Clinical Indications | Safety Concerns/Contraindications |
Centella asiatica (Gotu kola) |
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Vaccinium myrtillus (Bilberry) |
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Ginkgo biloba (Ginkgo) |
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Crataegus spp. (Hawthorn) |
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Aesculus hippocastanum (Horse Chestnut) |
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Conclusions: A Herbal Approach to Healing Pain & Inflammation
Herbal medicine offers clinicians numerous possible remedies for addressing a multitude of pain & inflammatory syndromes. Though a symptomatic approach to pain relief may be useful, it is crucial to ensure healthy resolution of the inflammatory response, tissue repair, and regeneration. More appropriate and efficacious than treating symptoms with herbal medicine, is taking an individualized systems-based approach to treatment, removing the underlying cause whenever possible, and addressing contributing layers of disease (e.g. stress, anxiety, vascular disease) in order to slow tissue-damaging processes and maintain tissue function. An important note for clinicians is also to adequately educate patients regarding their expectations of the use of herbs as anti-inflammatories & analgesics. Herbs are not drugs, and thus their effects will not be as fast-acting. Herbs offer a long-term solution to resolution of inflammation and are capable of controlling uncomfortable symptoms while nourishing underlying tissue imbalances, however their effects are often dose-dependent, and depending on the severity of the condition may require more frequent dosing and re-evaluation.