Topical analgesics are widely used for the
treatment of localized musculoskeletal and
neuropathic pain and represent an important
yet often omitted component of multimodal,
non-opioid pain management. By delivering
medication directly to the site of pain, topical
therapies can reduce systemic drug exposure
while maintaining therapeutic efficacy. Topical
analgesics encompass several pharmacologic
classes including counterirritants, capsaicin,
local anesthetics, nonsteroidal anti-inflammatory
drugs (NSAIDs), cannabinoids, and specialized
agents such as topical antidepressants. These
medications exert analgesic effects through
multiple mechanisms including, often containing
combinations of active ingredients that require
careful selection and evaluation by clinicians and
patients.
What is the difference between
topical and transdermal pain
medications?
Topical and transdermal medications are
frequently confused, yet they serve different
pharmacologic purposes. Topical medications
are intended to produce localized therapeutic
effects at the site of application, whereas
transdermal medications are designed to deliver
medications
systemically
through
dermal
absorption into the bloodstream.
Topical
analgesics
act
primarily
within
superficial tissues such as the skin, muscles, and
joints. Because systemic absorption is typically
limited, topical medications generally produce
fewer systemic adverse effects compared
with oral therapies, an often favored scenario
in the safety spectrum. This feature can be
particularly beneficial for patients at higher risk
of systemic medication toxicity, including older
adults, patients with gastrointestinal disease, or
individuals receiving multiple medications.1
The localized action of topical therapies makes
them particularly useful for conditions such as
osteoarthritis, minor musculoskeletal injuries,
and localized neuropathic pain syndromes.
Contemporary pain management guidelines
recommend topical analgesics as part of
a multimodal pain management strategy,
particularly when systemic medications may
pose additional safety concerns.2
What are the major classes of
topical pain medications?
Topical
analgesics
encompass
several
pharmacologic classes based on their mechanisms
of action. The most common categories include
counterirritants, capsaicinoids, local anesthetics,
NSAIDs, cannabinoids, and specialized agents
such as topical antidepressants.
Counterirritants are among the most widely
used ingredients in over-the-counter topical
pain products. These agents produce warming
or cooling sensations that alter pain perception
through sensory stimulation. Common examples
include cooling agents such as menthol or
camphor, along with warming agents such as
methyl salicylate, which are frequently found in
creams, gels, sprays, and patches marketed for
muscle and joint pain.
Local anesthetics represent another major class.
Lidocaine produces analgesia by non-selectively
blocking voltage-gated sodium channels in
peripheral nerves, thereby inhibiting the
transmission of pain signals. Anti-inflammatory
topical medications include NSAIDs such
as diclofenac, which inhibit cyclooxygenase
enzymes and decrease prostaglandin-mediated
inflammation and pain. Additional topical
therapies include capsaicin, which acts on
transient receptor potential channels involved
in nociception, and cannabinoid-containing
products, which produce effects within the
endocannabinoid system.3 Because many topical
products contain multiple active ingredients,
clinicians and patients should carefully review
product labels to identify pharmacologic
components and avoid unintended duplication.
How do counterirritants
relieve pain?
Counterirritants reduce pain through sensory
modulation
involving
temperature-sensitive
receptors in the skin. Two receptor systems play
a key role in this process: TRPV1 (warming)
and TRPM8 (cooling).
Capsaicin activates TRPV1 receptors, which
respond to heat and inflammatory stimuli.
Repeated stimulation of these receptors leads to
desensitization of nociceptive nerve fibers and
depletion of substance P, ultimately reducing
pain transmission.4
Cooling counterirritants such as menthol and
camphor activate TRPM8 receptors, producing
a cooling sensation that can temporarily
relieve discomfort. Menthol also demonstrates
dose-dependent pharmacologic effects; lower
concentrations may produce mild anesthetic
activity, whereas higher concentrations primarily
function as counterirritants.
These agents typically provide short-term
symptomatic relief and are commonly included
in combination topical products marketed
for muscle soreness, arthritis pain, and sports
injuries.
What is the clinical role of
capsaicin in pain management?
Capsaicin occupies a unique role among
topical analgesics because it produces analgesia
through neurochemical depletion of substance
P and desensitization of nociceptive nerve
endings by activating TRPV1.
76
FALL 2026 I RETAIL/COMMUNITY • SPECIALTY • LTC
Contributed by Mark Garofoli, PharmD, MBA, BCGP, CPE, CTTS
SCRATCHING MORE
Than the Surface
Than the Surface
A RE V IE W OF TOPIC A L PA IN ME DIC AT IONS