Pain is a sensory process involving a balance of inhibition and excitation of neuronal systems. Lack of inhibition or excitation of neuronal sensory systems can lead to pain. Maintenance of excitatory states such as in inflamed conditions, sets up a framework for chronic pain. Patients with a chronic pain state are predisposed to abnormal pain with relatively mild stimuli due to maintenance of the excitatory states. Chronic pain is thus the result of prolonged peripheral inflammation which is sensitive to NMDA (N-methyl-D-aspartame) antagonism. NMDA receptor activation leads to excitation and increase in pain transmission. Blocking the NMDA receptor with an antagonist such as dextrometorphan or ketamine results in pain relief to the patient.
As NMDA receptors play such a key role in neuropathic pain, an NMDA antagonist should be the first choice of therapy, a glutamate/AMPA agonist second and then either an alpha-2 agonist, alpha-1 antagonist or GABAβ agonist.
Why use Compounding Alternatives for Pain Management?
Optimal treatment for patients suffering from pain is essential. Uncontrolled pain prevents patients from working productively, enjoying recreation, or taking pleasure in their usual roles in the family and society. Chronic pain may have many different causes and perpetuating factors, making it much more difficult to manage than acute pain, requiring customised treatment protocols to meet the specific needs of each patient.
Treatment can involve the use of drugs which possess analgesic activity including antidepressants, anticonvulsants, anaesthetics and NMDA (N-methyl-D-aspartame) antagonists. By using these medications which act by different mechanisms of action in combination, smaller concentrations of each medication can be used.
Compounding also offers solutions to the limitations of commercial pain medications such as unique dosage forms, unavailable medications, bad tasting medicine and allergies.
Optional Dosage Forms Offered by Compounding
Topical/Transdermal delivery — gels, creams and solutions
Topical delivery systems offer the advantage of delivering the agent to the site of application thus avoiding the side effects associated with oral administration. Transdermal delivery systems are applied peripherally to skin, but act via systemic circulation. Both routes eliminate the “first-pass” effect avoiding hepatic metabolism. There is thus a decreased potential for drug interactions and low systemic levels of active agents. Transdermal delivery of pain medications can also often eliminate the need for injectable therapy.
Oral dosage forms — capsules, lozenges, flavoured oral suspensions
Oral doses can be made to incorporate medications into a single dose for ease of administration or simplification of a confusing dosing schedule.
Rectal preparations — suppositories
These formulations help overcome obstacles for patients who are unable to take medications orally (i.e. nausea, vomiting, altered consciousness, obstruction or difficulty swallowing). Its principal advantage is that it is independent of gastrointestinal tract motility and rate of gastric emptying.2
Nasal preparations — sprays
Nasal sprays can be used to deliver medication intranasally. Nasal drug delivery is a popular alternative route of administration for some systemically-acting drugs with poor oral bioavailability, and has advantages in terms of rapid onset on action and improved patient acceptability and compliance over other dosage forms.
Types of pain: Chronic and Acute
Acute and chronic pain are different clinical entities. Acute pain is provoked by a specific disease or injury, serves a useful biologic purpose, is associated with skeletal muscle spasm and sympathetic nervous system activation, and is self-limited.3
Acute pain may be caused by many events or circumstances, including:
- Broken bones
- Dental work
- Burns or cuts
- Labor and childbirth
Acute pain may be mild and last just a moment, or it may be severe and last for weeks or months. In most cases, acute pain does not last longer than six months and it disappears when the underlying cause of pain has been treated or has healed. Unrelieved acute pain, however, may lead to chronic pain.
Chronic pain, in contrast, may be considered a disease state. It is pain that outlasts the normal time of healing, if associated with a disease or injury. Pain signals remain active in the nervous system for weeks, months, or years. Chronic pain may arise from psychological states, serves no biologic purpose, and has no recognisable end-point.4 This is debilitating, expensive and affects everyone around the person experiencing the pain.
Common chronic pain complaints include:
- Low back pain
- Cancer pain
- Arthritis pain
- Neurogenic pain (pain resulting from damage to nerves)
- Psychogenic pain (pain not due to past disease or injury or any visible sign of damage inside)
Chronic pain may have originated with an initial trauma/injury or infection, or there may be an ongoing cause of pain. However, some people suffer chronic pain in the absence of any past injury or evidence of body damage.
The therapy of acute pain is aimed at treating the underlying cause and interrupting the nociceptive signals. The therapy of chronic pain must rely on a multidisciplinary approach and should involve more than one therapeutic modality.4
1. Neuropathic Pain
Neuropathic pain is a complex, chronic pain state caused by ectopic activity of the peripheral or CNS pain pathways and is not maintained by inflammation or tissue injury.5 With neuropathic pain, the nerve fibers themselves may be damaged, dysfunctional or injured. These damaged nerve fibers send incorrect signals to other pain centres. The impact of nerve fibre injury includes a change in nerve function both at the site of injury and areas around the injury.
One example of neuropathic pain is called phantom limb syndrome. This occurs when an arm or a leg has been removed because of illness or injury, but the brain still gets pain messages from the nerves that originally carried impulses from the missing limb. These nerves now misfire and cause pain.
- Shooting and burning pain
- Tingling and numbness
2. Arthritis — Osteoarthritis and Rheumatoid Arthritis
Arthritis is an ancient disorder that defies cure.6 Patients who respond to drug therapy often receive considerable benefit from a compounded preparation. Pain-relieving compounds that can be prepared in transdermal form, minimise the risk of adverse effects associated with some oral medications. Customised combinations and concentrations of analgesics also provide great benefits to these patients.
Osteoarthritis is a condition in which low-grade inflammation results in pain in the joints, caused by wearing of the cartilage that covers and acts as a cushion inside joints. As the bone surfaces become less well protected by cartilage, the patient experiences pain upon weight bearing, including walking and standing. Due to decreased movement because of the pain, regional muscles may atrophy, and ligaments may become more lax. OA is the most common form of arthritis. The word is derived from the Greek word “osteo”, meaning “of the bone”, “arthro”, meaning “joint”, and “itis”, meaning inflammation, although many sufferers have little or no inflammation.
Rheumatoid Arthritis (RA)
Rheumatoid arthritis is traditionally considered a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. It is a disabling and painful inflammatory condition, which can lead to substantial loss of mobility due to pain and joint destruction. RA is a systemic disease, often affecting extra-articular tissues throughout the body including the skin, blood vessels, heart, lungs, and muscles. About 60% of RA patients are unable to work 10 years after the onset of their disease.3
Symptoms — Osteoarthritis:
- Loss of movement
- Stiffness and swelling in the joints
- Snapping of the joints
- Bony growths at the joints and abnormal angulation
Symptoms — Rheumatoid Arthritis:
- Joint pain, there is usually pain in several joints
- Stiffness in the joints. You will usually see a reduction in the range of motion of affected joints
- Inflammation is common around affected joints. Signs of inflammation are redness, tenderness and warmth
- Swelling of affected joints and surrounding areas
- Small bumps called nodules may appear around affected joints
3. Palliative Care
Palliative care is any form of medical care or treatment that concentrates on reducing the severity of a disease. It is about a treatment to relieve rather than to cure and to help the patient live more comfortably by controlling pain and symptoms.
During the later stages of life when patients cannot take oral medications, compounded medications that can be administered rectally, topically, nasally or by oral inhalation may be more appropriate.7
A migraine is a vascular headache associated with changes in the size of the arteries within and outside of the brain. A migraine begins when hyperactive nerve cells send out impulses to the blood vessels, causing constriction, followed by the dilation of these vessels and the release of prostaglandins, serotonin, and other inflammatory substances that cause the pulsation to be painful. A migraine causes mild to severe pain and lasts from 4 hours up to a week.8
Migraines are associated with various combinations of neurologic, gastrointestinal and autonomic symptoms.
- Abdominal cramps
- Blurry vision
- Nasal stuffiness
The goal for postoperative pain management is to reduce or eliminate pain and discomfort with a minimum of side effects. There are many different ways to treat post-operative pain. For mild to moderate pain, oral painkillers may be sufficient. More severe pain is traditionally treated with injections of morphine or other opioids. If appropriate, local anaesthetics can be used to numb the nerves that transmit the pain from the operation area (e.g. epidural, nerve bundle to the leg or arm). Small surgical cuts can be infiltrated with local anaesthetic.
Ideally a combination of different drugs is used in lower concentrations, which improves efficacy and decreases the risk of side effects.
- General discomfort at or around the surgical site
- Sometimes pain can be accompanied by chills, fever, disorientation and vomiting
Acute Pain / Localised Injury
Acute pain has a well-defined cause, such as a cut, bruise, injection, burn or broken bone. Removing the cause will usually stop the pain.
(1) Jones Marty. Chronic neuropathic pain and opioid tolerance. Int J Pharm Comp. 2002 Jan/Feb; 6(1):4. (2) Standard for the Uniform Scheduling of Drugs and Poisons: No 24, June 2009. Published by the Australian Government under the Therapeutic Goods Act 1989. (3) Stevens Rom A, Ghazi Salim M. Routes of opioid analgesic therapy in management of cancer pain: The rectal route. Cancer Control: Journal of the Moffitt Cancer. 3rd Jan 2000. (4) Grichnik KP, Ferrante FM. The difference between acute and chronic pain. Mt Sinai J Med. 1991 May; 58(3):217-20. (5) Ford Peter R. Opioids: A review of the Pharmacology. Int J Pharm Comp. 2000 Jan/Feb; 4(1):17-20. (6) Marshall R et. al. Case Reports: Compounding to relieve arthritis pain. Int J Pharm Comp. 2008 Nov/Dec; 12(6):498-504. (7) Loyd V Allen, Int J Pharm Comp. 2000 July/Aug; 4(4):244. (8) http://www.webmd.com/migraines-headaches/guide/glossary-terms-headaches?page=4 (Accessed March 31st 2010) (9) http://www.health.nsw.gov.au/resources/publichealth/pharmaceutical/pdf/
prescriptions_nonhandwritten.pdf (Criteria for issuing non-handwritten (computer generated) prescriptions. Pages 7 and 9. Accessed November 23rd 2009)