Practice Directions Series New Solutions for Herbal Pain Manage ment
New Solutions for Herbal Pain Management Kerry Bone Founder and Director Research & Development MediHerb
New Solutions for Herbal Pain Management • • • •
Why treat pain? Is it valid to consider herbs for treating pain? The pharmacology of pain (briefly) Key herbs: Californian Poppy, Corydalis, Willow Bark, Ginger • Topical herbal treatments for pain management • Some major conditions: dysmenorrhea, low back pain, arthritic pain
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Why Treat Pain? What is Pain? According to Harrison’s Principles of Internal Medicine: • Pain is an unpleasant sensation localized to a part of the body • Any severe pain is accompanied by anxiety and the urge to stop it • Pain is a duality: it is both sensation and emotion
Why Treat Pain? Prevalence of Pain • A survey of Australian adults found chronic pain was reported by 17.1% of males and 20.0% of females1 • Most of these reported that the pain interfered with their daily lives • Prevalence of chronic pain tended to increase with age1 Reference 1 Blyth FM, March LM, Brnabic AJ et al. Chronic pain in Australia: a prevalence study. Pain 2001; 89(23): 127-134
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Why Treat Pain? • It is estimated that more than 60 million people in the United States suffer from some type of pain sufficient to significantly impact their lives2 • Almost $US5 billion is spent each year on surgery for chronic back pain alone2 • One in five Americans over age 60 takes medication to control pain, mainly for arthritis and low back pain3 References 2 Turk DC, Treatment of chronic pain: clinical outcomes, cost-effectiveness, and cost benefits. Drug Benefit Trends 2001; 13(9): 36-38 3 National Council on the Aging. Pain and older Americans survey major findings. PRNewswire June 9, 1997
Herbs for Pain? Can Herbs Play a Role in the Management of Pain? • Historically, they always have: opium, gelsemium, cannabis and aconite are examples • These are powerful and dangerous herbs and their therapeutic use is generally highly controlled • But recent research suggests that milder herbs can also play a valuable role • It must be remembered that control of pain is only one aspect of any treatment • The goal of phytotherapy is to treat and alleviate the cause wherever possible
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Pharmacology of Pain • Analgesics are divided into two classes: opiate (opioid) and non-opiate • Morphine and other opiate analgesics stimulate opiate receptors in the CNS and inhibit the perception of pain • Non-opiate analgesics inhibit the manufacture of chemicals that sensitize and/or stimulate pain fibers
Pharmacology of Pain Opiate Analgesics • Opiate analgesics are more effective for the sharp pain associated with the direct mechanical stimulation of pain fibers • They include morphine, codeine and related drugs • They are generally used to relieve intense pain
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Pharmacology of Pain Non-opiate Analgesics • Non-opiate analgesics are effective for alleviating the dull throbbing pain associated with such pathological processes as inflammation • They do not relieve the sharp pain associated with direct mechanical stimulation of pain fibers • They are (with the exception of acetominophen) anti-inflammatory agents
Pharmacology of Pain Non-steroidal Anti-inflammatory Drugs (NSAIDs) • NSAIDs suppress the signs and symptoms of inflammation, but do not alter the underlying causes • They include aspirin and modern drugs such as ibuprofen, indomethacin, Celebrex and Vioxx • They act by inhibiting prostaglandin (PG) synthesis by inhibiting the enzyme cyclooxygenase (COX)
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Pharmacology of Pain • NSAIDs are known to produce an analgesic effect in most inflammatory states • In addition to these peripheral actions, direct effects of salicylates within the CNS have also been described4 Reference 4 Bliddal H, Rosetzsky A, Schlichting P et al. A randomized, placebo-controlled, cross-over study of ginger extracts and Ibuprofen in osteoarthritis. Osteoarthritis and Cartilage 2000; 8: 9-12
Pharmacology of Pain COX-1 and COX-2 • It was recently discovered (1991) that there were two COX isoenzymes • COX-1 is constitutive and is involved in vital physiological functions. As such it is expressed on many somatic cells. • COX-2 is inducible and is expressed on inflammatory cells. Induction of COX-2 is a critical event in inflammation and pain.
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Pharmacology of Pain • Selective COX-2 inhibitors alleviate inflammation and pain and (in theory) will not cause the side effects associated with COX-1 inhibition (gastric damage, increased bleeding) • The reality is that COX-2 inhibitors do possess some activity against COX-1
Some Key Analgesic Herbs • Californian poppy and Corydalis can be seen as opioid-like analgesic herbs. However, their activity is likely to be very mild. • Willow bark and ginger can be likened to NSAIDs in their effects • Boswellia and turmeric are more anti-inflammatory and probably have little analgesic activity
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Californian Poppy
Californian Poppy • Eschscholtzia californica is a member of the poppy family and contains some typical alkaloids of this family • But the main alkaloids californidine and eschscholtzine are fairly unique to this species • According to Davis (of Parke-Davis) in the 1890s it was “an excellent soporific and analgesic, above all harmless” and “the effect produced . . . is the same as morphine . . .”
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Californian Poppy • Pharmacological studies have shown analgesic, sedative and anxiolytic activities • An extract formulation containing 80% Californian poppy and 20% Corydalis cava interacted with opiate receptors in vitro • High doses are needed for clinical analgesic activity
Corydalis
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Corydalis • Corydalis tuber (Corydalis ambigua) is commonly used in Chinese medicine for pain relief, especially organ pain • It contains around 20 alkaloids, but the most potent analgesic is tetrahydropalmatine (THP) • Analgesic potency is 1 to 10% of opium, depending on the study • THP does not interact with opioid receptors and appears to interact with the dopaminergic system
Corydalis • Clinical studies on THP have demonstrated analgesic effects in neuralgia, dysmenorrhoea and headaches • Use of extracts of the whole Corydalis tuber require repeated and high doses for analgesic effects (a total of 10 to 20 mL per day of a 1:2 extract) • THP is toxic in overdose, but use of Corydalis tuber is generally safe
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Willow Bark
Willow Bark • Many Salix species are used therapeutically especially Salix alba, S. daphnoides and S. purpurea • They all contain derivatives of salicylic acid, mainly salicin • Recent clinical trials have found that a high potency willow bark extract has significant analgesic activity, but with fewer side effects than conventional NSAIDs
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Practice Directions Series New Solutions for Herbal Pain Manage ment
The Differing Pharmacologies of the Salicylate Derivatives Aspirin • Aspirin is a potent inhibitor of COX-1 and COX-2 • The acetyl group causes irreversible acetylation of COX which inactivates it • Aspirin therefore has potent analgesic and antiinflammatory activities (COX-2) but also can cause gastric damage and inhibits platelet function (COX-1)
The Differing Pharmacologies of the Salicylate Derivatives
• Platelet function is inhibited by the inhibition of production of thromboxane A2 (a prostaglandin) by COX-1 • Because aspirin irreversibly inactivates COX by acetylation and because platelets cannot make new proteins such as COX (no nucleus) the effect of aspirin persists for the life of the platelet (7 to 10 days)
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Willow Bark: Salicin vs Aspirin COOH
COOH OH
CH2OH O
CH3
O
HO
OH O
OH CH2OH
O
Salicylic Acid
Aspirin
Salicin
The Differing Pharmacologies of the Salicylate Derivatives Salicylic Acid • Unlike aspirin, salicylic acid has virtually no inhibitory effect on isolated COX-1 or COX-2 • However it can inhibit PG synthesis in intact cells • This means that salicylic acid or sodium salicylate will have little antiplatelet (blood thinning) effects – they lack the acetyl group • However a high dose of salicylic acid irritates the stomach
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Practice Directions Series New Solutions for Herbal Pain Manage ment
The Differing Pharmacologies of the Salicylate Derivatives
• Recently, it has been reported that aspirin and sodium salicylate equipotently suppress COX-2 induction at therapeutic concentrations • Also salicylates appear to have direct analgesic effects in the CNS by unknown mechanisms
The Differing Pharmacologies of the Salicylate Derivatives Salicin • Salicin effectively delivers salicylic acid into the bloodstream, but it does this in a unique way • Salicin is carried unchanged (and hence is stomach friendly) to the distal ileum or colon where gut flora remove the sugar and convert it into salicyl alcohol
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Practice Directions Series New Solutions for Herbal Pain Manage ment
The Differing Pharmacologies of the Salicylate Derivatives
• The salicyl alcohol is absorbed and oxidized in the blood, tissue and liver to give salicylic acid • Salicin provides a more sustained release of salicylate than sodium salicylate itself
Willow Bark Proof of the Differing Actions of Willow Bark and Aspirin: • 35 patients were given either willow bark extract (delivering 240 mg of salicin per day) or placebo under double-blind conditions • Another 16 patients were given 100 mg of aspirin • The maximum arachidonic-acid-induced platelet aggregations were as follows: – willow bark 61.0 (± 21.6)% – placebo 78.0 (± 15.4)% – aspirin 12.7 (± 9.1)%
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Willow Bark • The inhibitory effect of willow bark extract on platelet aggregation was far less than aspirin and only marginally stronger than placebo (but was still statistically significant, p=0.04) • This means that willow bark is not a substitute for aspirin for blood thinning • However, since the mild effect was significant it should be used cautiously under close supervision with warfarin and NSAIDs
Willow Bark More Than Just Salicylate • A study involving 10 healthy volunteers found that a dose of a high potency willow bark extract (providing 240 mg/day of salicin) resulted in blood salicylate levels of around 1.4 µg/mL • In contrast, blood salicylate levels of 35 to 50 µg/mL have been reported after taking just 500 mg of aspirin • Clearly the clinically-observed analgesic effects from willow bark (see later) must come from more than just the effects of salicylate
© Kerry Bone
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Practice Directions Series New Solutions for Herbal Pain Manage ment
Willow Bark • Based on research on willow bark and related herbs it has been suggested that lipoxygenase and hyaluronidase inhibition and free radical scavenging effects, all from other components in willow bark, contribute to the overall analgesic effect • This means that many of the side effects, interactions and contraindications for aspirin, such as interactions with methotrexate, spironolactone and frusemide, are unlikely to apply for willow bark
Willow Bark Clinical Trials Osteoarthritis • In 78 patients with OA of knee and/or hip • Potent willow bark extract (containing 240 mg of salicin per day) versus placebo under double-blind conditions • The WOMAC pain index was used as the outcome after 2 weeks • It dropped by 14% for willow bark versus an increase of 2% for placebo (difference, p
