Adjuvants

Welcome to this video on adjuvants for the treatment of pain.

Adjuvants

Adjuvants are pharmacologic or non-pharmacologic therapies that are added to the primary analgesic to provide additive relief of pain or are used to provide independent relief of pain.

Let’s look first at adjunctive drugs, which are not usually marketed for the relief of pain but have analgesic properties.

Antidepressants are some of the most commonly used adjuvants. There are four different types:

• Tricyclic antidepressants
• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) AND
• Atypical antidepressants

Tricyclic antidepressants inhibit the uptake of serotonin and norepinephrine, and decrease pain signals sent to the brain.

Commonly used tricyclic antidepressants include:

• Amitriptyline
• Imipramine
• Doxepin AND
• Nortriptyline

Tricyclic antidepressants are mainstays in the treatment of chronic pain, which often responds poorly to opioids and other analgesics. Conditions for which tricyclic antidepressants may provide pain relief include:

• Neuropathy
• Arthritis
• Fibromyalgia
• Migraines
• Complex regional pain syndrome
• Chronic fatigue syndrome AND
• Irritable bowel syndrome

Selective serotonin reuptake inhibitors, such as fluoxetine (for example, Prozac) and paroxetine (Paxil) tend to be less effective than tricyclic antidepressants for chronic pain and are not effective for neuropathic pain.
However, they have fewer adverse effects and may provide some relief for other types of pain, especially if associated with depression, including:

• Arthritis
• Fibromyalgia
• Chronic fatigue syndrome AND
• Irritable bowel syndrome

Serotonin-norepinephrine reuptake inhibitors such as venlafaxine, duloxetine, and milnacipran HC are effective as adjuvants in the treatment of:

• Diabetic neuropathy
• Polyneuropathy
• Fibromyalgia AND
• Chronic musculoskeletal pain

Atypical antidepressants include:

• Mirtazapine, which is used for abdominal pain AND
• Trazodone, which is used for comorbid insomnia

Anticonvulsants, particularly gabapentin and pregabalin, are another class of drugs often used as adjuvants for neuropathy because they interfere with transmission of pain signals.

Conditions for which they are indicated include:

• Diabetic neuropathy
• Shingles
• Chemotherapy-associated nerve damage
• Herniated disk-associated nerve damage
• Trigeminal neuralgia

Next, corticosteroids, such as prednisone, methylprednisolone, and dexamethasone, reduce pain by decreasing inflammation, reducing blood flow, and inhibiting transmission of pain signals.

Corticosteroids are used in palliative care for mild to severe pain associated with bony metastasis, neuropathy, and visceral pain.

Antispasmodics, or muscle relaxants, are also used to reduce muscle spasms and associated pain. Smooth muscle antispasmodics, such as dicyclomine and hyoscyamine, are used to reduce intestinal, gastric, and bladder spasticity such as with IBS and interstitial cystitis.

Skeletal muscle antispasmodic, such as cyclobenzaprine (Flexeril), tizanidine, and carisoprodol, are used to reduce neurological spasticity, such as with cerebral palsy, multiple sclerosis, and spinal cord disorders.

Another class of adjuvants is bisphosphonates, such as

• Alendronate AND
• Pamidronate

Bisphosphonates are used in cancer to reduce pain associated with bony metastasis because they inhibit bone resorption and reduce the growth of cancer cells.

Some topical preparations are also used to reduce pain. These include:

• Lidocaine, a topical anesthetic, that may reduce pain from procedures and from minor burns, abrasions, and insect bites. AND
• Capsaicin, which first stimulates and then decreases pain signals, is used for a wide range of pain disorders, including:
• Arthritis
• Neuropathy, including post-herpetic neuralgia, diabetic neuropathy, and trigeminal neuralgia AND
• Skin conditions, such as psoriasis

Botulinum toxin (Botox®) is a powerful neurotoxin that is injected into muscle tissues to relax skeletal muscles and inhibit the release of the neurotransmitter acetylcholine, thereby reducing the transmission of pain signals.

Botulinum toxin is used to treat arthritis, neuropathic pain, migraines, and myofascial syndrome.

N-methyl-D-aspartate (NMDA) receptor antagonists, are another class of adjuvants that can provide relief for acute and chronic pain. These include:

• Ketamine, which may be used to reduce the dosage of opioids required to treat pain or for those with opioid resistance.
• Methadone, which is used for opioid resistance and neuropathic pain AND
• Dextromethorphan, which is used for neuropathic pain.

Medical cannabis (better known as marijuana) has been used legally and sometimes illegally for decades to control chronic pain associated with nerve pain and muscle spasticity, such as in multiple sclerosis and Parkinson’s disease.

Cannabidiol (CBD) is a non-intoxicating extract of hemp that reduces the transmission of pain as well as increases dopamine, which reduces the sensation of pain. CBD is not yet legal in all states.

Uses of CBD include:

• Pain (various types)
• Inflammation
• Chemotherapy-induced nausea and vomiting

Nonphacological Options

In addition to pharmacological adjuvants, a number of nonpharmacological adjuvants are used to control pain:

First, acupuncture, which uses small needles to stimulate pressure points, enhances production of natural endorphins and releases corticosteroids to help relieve pain.

Then, massage relieves pain by relaxing muscles, increasing circulation, increasing production of endorphins, and reducing stress.

Next, relaxation, visualization, and mindfulness exercises may help to reduce stress and relieve chronic low back pain, arthritis, and other non-malignant as well as malignant types of pain.

Thermal therapies, such as hot and cold therapy, are commonly used to reduce inflammation, relax muscles, and relieve pain.

Cold is usually used for the first 24 to 48 hours of injury and then heat. For chronic pain, some respond better to cold and some to heat:

• Cold therapy relieves osteoarthritis, gout, strains, sprains, and tendinitis, and low back pain
• Heat therapy relieves osteoarthritis, strains, sprains, tendonitis, stiff muscles, and muscle spasms

Hypnotherapy may be used to control both acute and chronic pain, reducing the need for analgesia and sedation.

Finally, transcutaneous electrical nerve stimulation (TENS) uses a mild electric current to reduce pain associated with injured nerves and joints, such as back pain, joint pain, arthritis, and labor and delivery pain.

There are many options for controlling pain and reducing the use of opioids. Adjuvant medications and therapies have important roles in pain management and especially in improving the quality of life in those with chronic pain.

Thanks for watching, and happy studying!