Addressing Pain with Phyto-Therapy: A Scientific Perspective

According to the National Institutes of Health, “pain affects more Americans than diabetes,
heart disease and cancer combined” (1). Uncontrolled pain is debilitating, and can lead to
secondary conditions such as anxiety, depression, and sleep disruption (2, 3). Oftentimes,
conventional treatments are not adequate for controlling pain (4, 5, 6), which leads many to
explore alternative treatments including aromatherapy (7). Fortunately, evidence for
alternative treatments is mounting, and these data add to the scientific understanding of the
complex mechanisms of acute, chronic, and neuropathic pain.

This review explores the analgesic and anti-inflammatory aspects of chemicals found in some
aromatics, and their interaction with cellular processes in the body. It is the opinion of this
author that the future of aromatherapy lies in integration of scientific data. This not only
increases the likelihood of effective treatments, but also lends legitimacy to aromatherapeutic
practice as a whole. Continued collaboration of bench scientists, physicians, and
aromatherapists is crucial in complementary medicine, and improvement of quality of life for
those living with pain.


Cells communicate and collect information about their environment to determine the best time
to grow, divide, or undergo any number of changes. This is accomplished via binding of
extracellular signals received at the cell membrane. These extracellular signals are called
ligands, and they bind to special cellular protrusions called cell receptors. Receptors in nerve
fibers, called nociceptors, act as alert systems for damaging stimuli, which includes
temperature extremes and the presence of chemicals (8). Once a stimulus is detected,
nociceptors excite nerve fibers, which send information to the central nervous system (9).
This heightens the sensitivity of the nerve to temperature and touch (8), and prompts the
individual to eliminate the offending stimulus (10). Sensitization leads to allodynia (when
non-painful stimuli evoke a pain response), and hyperalgesia (increased sensitivity to pain)
occurs when the threshold for nociceptor activation falls (10). This may be the cause of
chronic pain syndromes like fibromyalgia.

An important receptor involved in pain is the TRPV1 receptor (also called the capsaicin
receptor or vanilloid receptor) (8). Capsaicin in chili pepper CO2, gingerol in ginger CO2
extracts, and piperine in black pepper CO2 extracts bind TRPV1 (11, 12, 13), causing tingling
and pain. However, prolonged exposure to these substances leads to reduced TRPV1 activity due to desensitization (12). In this manner, products containing these extracts work to reduce pain. Capsaicin-containing over the counter products and aromatherapeutic formulations have been successful topical analgesics for decades (14).

Two other important receptors are TRPA1 and TRPM8, which are involved in cold detection.
The TRPA1 receptor detects noxious cold and a number of other stimuli, while TRPM8
detects cool temperatures (15, 16). Both receptors are activated by menthol, resulting in a cold sensation. A number of substances have been identified as analgesic compounds that
interact with TRPA1 and TRPM8, including camphor, 1,8-cineole, and Eucalyptus globulus
essential oil (16). However, activation of TRPA1 is best avoided for pain relievers because it
can also cause pain in some cases. As such, menthol has limitations as a pain reliever. While
camphor inhibits TRPA1 and activates TRPM8, it also activates TRPV1, and produces a “hot” sensation (16). Camphor additionally has numerous safety concerns. Convulsions, kidney and brain damage, and serious poisoning pose a risk in a dose-dependent manner to children (17). 1,8-cineole inhibits TRPA1, reversing effects of menthol-activated TRPA1 receptors, and activates TRPM8 (16). 1,8-cineole containing E. globulus essential oil showed similar activity, and both exhibit significant pain relief in the clinical setting (14). As such, 1,8-cineole is a better choice for TRPA1/TRPM8 receptor mediated analgesia.

TRPV1 receptors colocalize with CB1 and CB2 receptors, which are part of the
endocannabinoid system (18), and there is overlap in ligand binding of TRPV1 and CB2 (19).
The endocannabinoid system is involved in responses to hormones and neurotransmitters
and is essential in formation and maintenance of interneuronal communication (20).
Endogenous cannabinoids, such as anandamide (also found in chocolate) and many
phytocannabinoids, bind CB1 and CB2 receptors variably. Cannabidiol (CBD), a
phytocannabinoid, does not bind to the CB1 receptor but does bind to CB2. CBD as well has
varied medical applications, including pain relief and mood regulation.

Beta-caryophyllene (BCP) is a sesquiterpene found in many essential oils, including black
pepper, balsam copaiba, cannabis (sativa) and sweet basil, and also binds the CB2 receptor
(17, 19). BCP relieves both acute and chronic pain in vivo (19). CB2 ligands (including
beta-caryophyllene) can stimulate release of beta-endorphins that bind opioid receptors and
also inhibit inflammatory factors (19). As such, CB2 ligands interact with the opioid and
inflammatory system in addition to the endocannabinoid system (19).


Inflammation is concurrent with nociceptor stimulation and is an inherently protective
mechanism that removes damaged tissue and infection before initiating repair (21). Tissue
damage triggers the release of pro-inflammatory cytokines, chemokines, and prostaglandins
(3, 8, 10, 22). Well-described cytokines include TNF-alpha (tumor necrosis factor alpha),
which has been implicated in acute inflammatory responses as well as chronic inflammatory
conditions (10). Treating inflammation is often a first step to reduce pain (10, 14).

Non-steroidal anti-inflammatories (NSAIDs), such as aspirin, ibuprofen, and diclofenac, are
usually the first line of medications used to control pain. NSAIDS block prostaglandin
synthesis, thereby reducing inflammation (10, 21, 23) and may also interact with
neuro-modulating opioid peptides and neurotransmitters (23). New medications, like
etanercept, control inflammation by blocking inflammatory molecules from binding to their receptors (8). These medications reduce hyperalgesia in in vivo inflammation models as well
as in patients with rheumatoid arthritis (8, 10).

Many aromatics reduce inflammation in the clinical setting, 1,8 cineole, for example, reducing
inflammation of the colon in vivo in model organisms (14). 1,8-cineole was also shown to
definitively suppress cytokine production, which in turn reduces inflammation (24, 25).
Eucalyptus globulus essential oil, which typically is the essential oil highest in 1,8-cineole
(17), both prevents inflammation and reduces inflammation in vitro (25).

Beta caryophyllene (BCP) is another powerful anti-inflammatory (19, 26). BCP blocks the
release of pro-inflammatory TNF-alpha and prostaglandins and reduces levels of both
beta-endorphins (involved in inflammation and pain) and interleukin 1 beta, a cytokine (19,
27, 28). Because BCP binds CB2 receptors and reduces inflammation, it has both analgesic
and anti-inflammatory properties (19, 26, 28). Black pepper essential oil (BPEO) is very high
in BCP (17), and has anti-inflammatory, antioxidant, and analgesic properties (29). BPEO
was effective in inhibiting inflammation in acute inflammation as well as chronic inflammation
in vivo models (29). This is consistent with previous studies that established BPEO and
capsicum extracts containing capsicin possess anti-inflammatory, antioxidant, and
anti-cancer properties (30).

Aromatic Formulation

To formulate a topical pain reliever, the most effective method would be to include aromatics
with both anti-inflammatory and analgesic effects. Aromatics high in cannabidiol (CBD),
capsaicin, menthol, 1,8-cineole, beta caryophyllene (BCP), gingerols, or piperine may be the
most effective choices. As such, this author suggests incorporation of chili pepper CO2 total
extract, ginger total extract, or black pepper CO2 extract to stimulate the TRPV1 receptor and
induce tingling and heat initially. TRPV1 signal is then desensitized, and results in reduced
TRPV1 activity, and pain relief.

Choosing a menthol-containing aromatic, such as peppermint essential oil, will provide a
cooling sensation because of its interaction with the TRPA1 and TRPM8 receptors.
Peppermint essential oil also contains 1,8-cineole, which has additional TRPM8 activity.
Incorporating an essential oil like Rosemary CT 1,8-cineole provides high levels of the
TRPM8 active chemical, but also moderate levels of BCP. Black pepper essential oil is a
favorite for pain relief due to its high BCP content, which interacts with the CB2 receptor and
the opioid system. This essential oil has both anti-inflammatory and analgesic effects due to
its chemistry.


Consideration of the client’s clinical symptoms will guide aromatic choices, and adjusting the
concentration of each aromatic component will tailor the blend to the unique clinical symptoms. Because the thalamus in the brain analyzes smell and also perception and
interpretation of pain, a significant aspect of pain is the psychological aspects. As such,
incorporation of aromatics that address stress and pleasure will enhance effectiveness of the
formula. By understanding the underlying cellular and chemical interactions of cell receptors
and aromatic chemicals, aromatherapeutic professionals are better able to achieve true pain
relief for their clients.

Table 1. Representative aromatics containing analgesic and anti-inflammatory compounds


Shannon Becker PhD, RA

Shannon's mission is to combine scientific training with advanced aromatherapy training, to help others and further advance evidence-based aromatherapy. She has written scientific articles detailing the biological and chemical properties of essential oils and aromatic compounds, and served as a peer reviewer for the International Journal of Professional Holistic Aromatherapy. Shannon has joined the Institute of Holistic Phyo-Aromatherapy faculty, and serves on its Advisory Board. Click Here to Learn More About Shannon Becker.


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