Topical Analgesics: Spreading the Word

Spreading the Word

Pat Morley-Forster, MD, FRCP(C)
Professor, Department of Anesthesiology and Perioperative Medicine
Schulich School of Medicine, Western University, London, Canada

Topical analgesics have been widely used in Europe for decades, but only recently are becoming popular in North America. Many doctors are not aware of how effective they can be for a variety of painful conditions. They are formulated as creams, gels, sprays or patches.

Many medications nowadays are delivered by a patch. It is important to understand the difference between a patch or a cream that works topically versus one that is transdermal. A transdermal patch delivers the active drug to the bloodstream by means of absorption into the blood stream with the intended site of action being on the central nervous system. For example, fentanyl is a transdermal patch. But a topical pain-reliever is intended to act on the pain receptors within the skin and underlying tissue. As a safety feature, very little enters the bloodstream.

As the drug does not reach the brain, or any other organs, the main benefit of a topical analgesic is that there are unlikely to be side effects or drug interactions. This is especially important in the elderly, and in those who are on multiple medications. Other advantages to a topical are that it can be easily used as needed, and is useful when oral intake may not be possible.

The type of gel or “vehicle” in which the analgesic drug is mixed must be able to penetrate skin, which is a highly effective barrier. The gel must be both water and fat-soluble to penetrate multiple layers in the skin. Not surprisingly, there is a great deal of variability between individuals in skin characteristics, such as gender, age, race, temperature. Enzymes within the skin may inactivate the drug by breaking it down. And there is always the small chance of skin irritation, either from the active drug, or from the vehicle. Covering the skin with a dressing improves penetration and can make the pain relief last longer.

Inflammation, such as occurs with joint arthritis, tendonitis, or acute muscle strain, increases certain chemical messengers in the area, and these pain signalers are sensed by nerve endings (receptors) in the skin. The nerves carry the message of inflammation to the spinal cord, and from there to the brain, which interprets it as pain. There has been a great deal of research on the use of non-steroidal anti-inflammatory (NSAID) topical products, involving thousands of patients in North America and Europe. Some are available over-the-counter (OTC), some only by prescription. When anti-inflammatories (NSAIDS) are taken as a pill, they often cause stomach upset and can interact with blood thinners These side effects do not happen when the NSAID is applied to the skin. Local skin reactions are also rare.

Topical gels containing NSAIDs may take several days to reach their full effects. The most commonly studied NSAIDs have been ketoprofen, diclofenac, indomethacin, ibuprofen, and salicylates. They have been used successfully for acutely painful conditions such as soft tissue trauma, sprains, as well as osteoarthritis, and rheumatoid arthritis. Randomized placebo-controlled trials in North America of topical diclofenac for knee osteoarthritis have reported benefits on pain and function scores after 4 and 12 weeks, equivalent to taking the NSAID in pill form.

The NSAID, diclofenac, is available in Canada by prescription as Pennsaid® (1.5% solution).  Despite its freedom from side effects in the elderly, it is not covered by provincial drug benefits in Ontario, though may be in other provinces. It is also available in a slightly weaker OTC preparation called Voltarenmulgel (diclofenac 1.16%). 

Other common classes of drugs used in topical analgesics are capsaicin, local anesthetics, and counterirritants. Research trials have also been carried out on ketamine.  A small study of 20 patients from Australia found that after application of 10% topical ketamine there was a reduction in hypersensitivity to touch in patients with complex regional pain syndrome. Serum levels of ketamine were barely detectable.

A doctor can write a prescription for a topical, which combines several types of pain relievers together into one gel. This script must be filled at a pharmacy, which has a license to compound pharmaceutical products (referred to as a compounding pharmacy).

Capsaicin, the active ingredient in chili peppers, is available both OTC and by prescription in different strengths. It works by blocking specific channels on nerve fibers that are necessary for sensing pain. The lower concentration (0.025%) is effective for arthritis pain while the higher one (.075%) is more commonly prescribed for neuropathic pain, such as shingles. The major problem with capsaicin is that for the first few days it causes intense burning. Since burning pain is often the symptom that is being treated, it is difficult for many people to feel worse burning while waiting several days for the relief to start.

Recently an 8% capsaicin patch (Qutenza®) has been released in the United States, though not yet in Canada. A single application of this high strength capsaicin product may provide relief for weeks. A randomised, double-blind study in patients with shingles showed that a 60 minute application of the 8% patch resulted in sustained relief greater than the placebo for up to 12 weeks.

Another class of drugs that may be helpful for neuropathic pain are local anesthetics. Local anesthetic gels or patches can calm hypersensitive nerves in the skin by blocking them from firing. In the United States, a patch embedded with the local anesthetic lidocaine (Lidoderm®) has been available for almost 15 years. Research has proven it as effective for up to 12 hours in shingles pain, diabetic nerve pain and, also, knee arthritis. As it is not yet available in Canada, doctors sometimes prescribe lidocaine 5% gel as an alternative. This compounded product requires a prescription in Canada, whereas the Lidoderm® patch in the United States does not.

In research trials of Lidoderm®, reductions in pain scores of over 50% have been reported in a significant number of patients. Up to 4 patches on different areas of the body can be applied daily without causing levels of lidocaine in the blood that would be of concern. The Canadian Pain Society Guidelines for neuropathic pain treatment recommend lidocaine as second –line therapy, after gabapentin. It is fairly expensive. The Pharmacological management of chronic neuropathic pain – Consensus statement and guidelines from the Canadian Pain Society Guidelines.

Counterirritants are another class of topical analgesics that  help relieve muscle pain, in particular, though may help modestly with joint or nerve pain These include camphor, menthol, garlic , and peppermint and eucalyptus oil. They work by irritating nerve endings in the skin due to causing changes in temperature or acidity, causing the nerve to interpret a strong sensation of burning or coldness.  The overstimulation over several minutes desensitizes the nerves. Combining an effective analgesic with a counterirritant often works more effectively than using just one active drug. An example of this would be RUB A 535®, which combines capsaicin, salicylate and the counterirritants camphor and menthol.

The availability of topical analgesics is increasing quickly. While they do not work for pain in every situation or relieve all of the pain, they are quite safe, and free of long-term side effects (View available over-the-counter options in Appendix I).

References

  1. Stanos SP. Topical agents for the management of musculoskeletal pain.  J Pain Symptom Manage. 2007;33(3):342-355.
  2. Sawynok J. Topical analgesics in neuropathic pain. Current Pharmaceutical Design. 2005(11):2995-3004.
  3. De Leon-Casasola OA. Multimodal approaches to the management of neuropathic pain: The role of topical analgesia. J Pain Symptom Manage. 2007;33:356-364.
  4. Bookman AA, Williams KS, Shainhouse JZ. Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: A randomized controlled trial CMAJ. 2004;171:333-338.
  5. Binder A, Bruxelle J, Rogers P, et al. Topical 5% lidocaine (lignocaine) medicated plaster treatment for post-herpetic neuralgia: results of a double-blind, placebo-controlled, multinational efficacy and safety trial. Clin Drug Investig. 2009;29:393-408.
  6. Mason L, Moore Ra, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004;328:991.
  7. Backonja M, Wallace MS, Blonsky R, et al. NGX-4010, a high concentration capsaicin patch, for the treatment of post-herpetic neuralgia: A randomized double-blind study. Lancet Neurol. 2008;7:1106-12.

 

APPENDIX 1:

This appendix summarizes most of the topical preparations currently available in Canada.

Your doctor may have his or her favorite” recipe” that does not appear on this list.

Over the counter products:

RUB A535 (salicylate, capsaicin, camphor, salicylate)
Aspercreme (Salicylate 10%))
Ben-Gay (salicylate, menthol,camphor)
Biofreeze (menthol 10%)
Lakota (Capsaicin )
Lidoderm Patch (only available in US)
Tiger Balm  (capsaicin and camphor)
Voltaren Emulgel  (diclofenac  (1.16%))

Prescription Products:

Pennsaid (diclofenac 1.5%)
Qutenza(capsaicin 8%)

Compounded  products :
(require prescription and compounding pharmacy)

Amitriptyline/Ketoprofen 7.5%/lidocaine  5%
Ketamine 5 or 10%
Lidocaine 5 or 10%