Pharmacology of Analgesia and Pain Relief

Introduction to the Pharmacology of Analgesia and Pain Relief

• Analgesia and pain relief have complex pharmacology.
• The core principle of treatment focuses on understanding the biological basis of pain.

Learning Objectives

• Students will learn about the different types of pain experienced by patients.
• They will understand general treatments for nociceptive pain.
• They will learn about general treatments for neuropathic pain.
• They will also learn about local anesthesia techniques used in dental procedures.

Pain Definition and Transmission

• The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage.
• Sensory nerve signals travel through the spinal cord to the cerebrum and are perceived as sensations in the cerebral cortex.
• Pain is a subjective experience varying among individuals.

Types of Pain

• Nociceptive pain: Caused by the activation of nociceptors in response to thermal, mechanical, or chemical stimuli.
  • Can range from superficial to deep.
  • Examples include soft tissue damage, infection, and inflammation.
• Neuropathic pain: Arising from damage or disease to the nervous system.
  • Can result from conditions like stroke or cancer.

Treatment of Nociceptive Pain

• NSAIDs (Nonsteroidal Anti-inflammatory Drugs):
  • Work by inhibiting the enzyme cyclo-oxygenase (COX), reducing prostaglandin production, and lessening inflammation and pain.
  • Two types: 1-block COX-1 and COX-2, and 2-block COX-2 only
  • Examples: aspirin, ibuprofen, piroxicam, mefenamic acid, diclofenac, ketoprofen, indomethacin, and naproxen.
  • Suitable for general aches, dental pain (e.g. post-extraction), period pain, headache, hangovers, arthritis, musculo-skeletal pain.
• Side effects: Can cause stomach irritation or ulcers in severe cases. Ibuprofen generally carries the lowest risk, while naproxen carries a higher risk. NSAIDs may trigger asthma attacks in sensitive individuals. Patients with aspirin allergies should avoid all NSAIDs. Aspirin should not be given to children under 16 to avoid Reye's syndrome.
• Paracetamol/Acetaminophen:
  • Has analgesic and antipyretic effects similar to aspirin and ibuprofen, but has limited anti-inflammatory properties.
  • Side effects generally are less severe than NSAIDs but can be fatal in overdose. Use with caution in liver impairment.

Treatment of Nociceptive Pain - Opioids

• Opioids (narcotics) are substances that act on opioid receptors in the brain, spinal cord, and gastrointestinal (GI) tract.
• Isolated from the opium poppy; natural ligands endorphins and enkephalins also function as pain killers.
• Opioid receptors are sub-divided into mu (μ), delta (δ), and kappa (κ) receptors.
• Analgesic effects are primarily due to action on μ-receptors; side-effects result from action on μ, δ and κ receptors.
• Side effects
  • euphoria;
  • convulsions;
  • dysphoria (dissatisfaction with life)
  • respiratory depression, physical dependence, nausea and vomiting,
  • pupil constriction, sedation (pinpoint pupil)

General Treatment Rules for Opioids

• Start with non-opioids (e.g., codeine, either alone or in combination with NSAIDs).
• Monitor the balance between efficacy and side effects.
• Typically used post-operatively (short-term) or for cancer-related pain (long-term).
• Start at a low dose (20-30 mg daily orally) and increase as needed.

Specific Properties of Codeine and Morphine

• Codeine and diamorphine are pro-drugs that are converted to morphine in the body.

• Intact codeine/diamorphine bind less effectively to opioid receptors than morphine.

• Codeine requires the liver enzyme CYP 2D6 to create morphine (about 10% conversion rate).

• Patients lacking this enzyme will not experience the analgesic effect of codeine.

• Diamorphine is more lipophilic than morphine, facilitating quicker CNS penetration.

• Hydrolysis of diamorphine produces 6-acetyl morphine which is more potent at mu receptors. Overall, diamorphine is typically found to be more effective.

Treatment of Neuropathic Pain

• Neuropathic pain is more challenging to treat than nociceptive pain because the underlying causes and biological processes are less well understood.
• Initial treatment typically follows the same procedure as for nociceptive pain (trial-and-error method).
• Some drugs developed for other purposes, such as gabapentin and pregabalin (anti-convulsants) and amitriptyline (anti-depressant), may have some effect on neuropathic pain.
• However, severe side effects may be encountered, including sedation and confusion.

WHO Pain Ladder

• A pain-management framework created to provide a structured approach to pain treatment based on increasing intensity and potential complexity of the pain.
• It is a step-wise method. Start with non-opioids, then progress to opioids, and consider adjuvant analgesics for improved management.

Anaesthesia

• Anaesthesia is characterized by a loss of sensation (or inability to feel) pain.
• Used to prevent pain during surgery.
• Types:
• General anesthesia: complete loss of sensation with unconsciousness.
• Local anesthesia: loss of sensation in a specific area of the body (e.g., dental procedures).

Dental Local Anesthetics

• Lidocaine: The primary agent.
• Mechanism of action:
  • Lidocaine's tertiary nitrogen group partially ionizes in the aqueous environment of the injection solution.
  • The un-ionized form diffuses into nerve cells.
  • Inside the nerve cell, lidocaine re-ionizes which blocks sodium channels.
  • This prevents sodium influx which, in turn, stops action potentials and nerve impulses; thus the pain signal doesn't reach the brain.
• Duration of action: Typically a few hours.
• Epinephrine: Often combined with local anesthetic to prolong its duration by reducing blood flow from the injection site.

Conclusion

• Effectively managing pain and anesthesia involves complex pharmacologies and biological understanding.
• Pain treatment generally begins with NSAIDs and progresses to opioids, if necessary.
• Side effects are a consideration.