Introduction

• Pain is a complex and subjective experience involving both physiological and psychological aspects.
• Nociception refers to the process of transmitting signals related to potentially harmful stimuli from the body to the brain.
• Pain can be classified into:
  • Nociceptive pain: Originates from tissue damage.
  • Neuropathic pain: Results from damage to the nervous system.
  • Mixed pain: A combination of nociceptive and neuropathic pain.
• Analgesics are medications designed to alleviate pain by targeting various stages of the pain pathway.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• NSAIDs are a diverse group of medications used to reduce pain, fever, and inflammation.
• They are commonly prescribed for conditions like muscle pain, menstrual cramps, arthritis, fever, gout, migraines, and pain management after acute injuries.
• NSAIDs work primarily by inhibiting cyclooxygenase (COX) enzymes, which are involved in the production of prostaglandins.

Mechanism of Action

• Prostaglandins are lipid compounds that play roles in inflammation, pain, and fever.
• Two main types of COX enzymes:
  • COX-1: Found in most tissues, regulates normal bodily functions.
  • COX-2: Produced primarily in response to injury and inflammation.
• NSAIDs block COX enzymes, decreasing prostaglandin production, which reduces pain and inflammation.

Classification of NSAIDs

• NSAIDs are classified by their chemical structure and selectivity for COX-1 or COX-2.
• Non-selective NSAIDs inhibit both COX-1 and COX-2.
• Selective NSAIDs primarily inhibit COX-2, influencing their side effect profile.

Types of NSAIDs

1. Acetylated Salicylates

   • Aspirin: At low doses, it inhibits COX-1, providing antiplatelet effects; at higher doses, it inhibits both COX-1 and COX-2 for pain relief.

2. Non-acetylated Salicylates

   • Includes diflunisal and salsalate.

3. Propionic Acids

   • Includes ibuprofen and naproxen.

4. Acetic Acids

   • Includes diclofenac and indomethacin.

5. Enolic Acids

   • Includes meloxicam and piroxicam.

6. Anthranilic Acids

   • Includes meclofenamate and mefenamic acid.

7. Naphthylalanine

   • Includes nabumetone.

8. Selective COX-2 Inhibitors (Coxibs)

   • Developed to primarily target COX-2, theoretically reducing gastrointestinal side effects. Examples include celecoxib and etoricoxib.

Administration of NSAIDs

• NSAIDs are available in various formulations:
  • Oral: Tablets, capsules, liquids.
  • Topical: Creams, gels, patches.
  • Parenteral: Intravenous (IV).
• Topical NSAIDs provide targeted pain relief with reduced systemic side effects.

Place in Therapy

• The choice of NSAID depends on:
  • The specific condition being treated.
  • The patient’s medical history and risk factors.
  • Potential drug interactions.
  • Patient preference and experience with NSAIDs.
• Long-term use of NSAIDs requires regular monitoring for potential adverse effects.

Paracetamol (Acetaminophen)

• Paracetamol, also known as acetaminophen, is one of the most widely used analgesics worldwide.
• Effective for mild to moderate pain and fever but has limited anti-inflammatory properties.

Mechanism of Action

• The exact mechanism is not fully understood.
• It is thought to work by indirectly inhibiting COX enzymes, particularly in the central nervous system.
• May have weak effects on COX-3, a variant of COX-1.
• Other proposed mechanisms include interactions with the serotonergic and cannabinoid systems involved in pain modulation.

Administration of Paracetamol

• Available routes:
  • Oral: Tablets, capsules, liquids.
  • Rectal: Suppositories.
  • Intravenous (IV).

Place in Therapy

• Often used as a first-line agent for mild to moderate pain and fever.
• Frequently combined with other analgesics, including NSAIDs and opioids, for enhanced pain management.

Topical Analgesics

• Topical analgesics are applied directly to the skin for localised pain relief.
• Benefits include:
  • Targeted delivery to the painful area, minimising systemic side effects.
  • Improved patient compliance, especially for those with difficulty swallowing pills.

Types of Topical Analgesics

1. Topical NSAIDs

   • Work by inhibiting COX enzymes locally, reducing prostaglandin production at the application site.
   • Examples include diclofenac, ibuprofen, ketoprofen, and salicylate preparations.

2. Capsaicin

   • Derived from chilli peppers, capsaicin initially stimulates and then desensitises sensory nerves, effective for neuropathic pain.

3. Local Anaesthetics (LAs)

   • Provide temporary numbness by blocking nerve impulse transmission.
   • Available in creams, gels, patches, and injections. Examples include lidocaine.

Place in Therapy

• Generally safe and effective for mild to moderate pain.
• Can be used alone or as part of a multimodal pain management strategy.

References

1. Grainger, J., & Tenny, S. (2020). Pain Management. In StatPearls. StatPearls Publishing. Retrieved from NCBI

2. Ruel, R. M., & Sharma, S. (2021). Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). In StatPearls. StatPearls Publishing. Retrieved from NCBI

3. Truter, I. (2019). The use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of cardiovascular events: A review. South African Family Practice, 61(3), 26-30. Retrieved from Taylor & Francis Online

4. Ballantyne, J. C. (1999). Opioids for chronic pain: Taking stock. Journal of Pain and Symptom Management, 17(2S), S1-S12. Retrieved from SAGE Journals

5. Singh, P., & Bhardwaj, A. (2020). An overview of analgesics: NSAIDs, paracetamol, and topical analgesics. Journal of Pharmacological Research, 15(2), 45-54. Retrieved from ResearchGate