Pain Management and Analgesics

Pain and Nociception

• Nociception is the detection of noxious stimuli.
• Transmission of noxious information occurs to the spinal cord and brain.
• Sensitization and modulation of nociceptors occur.
• Transmission at spinal level is regulated.
• Nociception regulation is vital.

Analgesic Drugs

• Analgesic drugs inhibit pain sensation.
• Descending inhibition of nociception is boosted by analgesic drugs.
• Central and peripheral sensitization is inhibited by analgesic drugs.

Opiate Drugs

• Opiate drugs are opioid receptor agonists.
• They mimic endogenous opioids.
• Examples include morphine, heroin (diamorphine), codeine, methadone, pethidine (etorphine), fentanyl, remifentanyl, butorphanol, and buprenorphine.
• Naloxone is a μ, δ, κ antagonist.

World Health Organisation Pain Ladder

• Mild pain is managed with NSAIDs (e.g., aspirin, ibuprofen).
• Moderate pain is managed with codeine or buprenorphine.
• Severe pain is managed with morphine or fentanyl.

Central Sites of Analgesia

• Opiates activate the midbrain periaqueductal grey, medulla nucleus raphe magnus, and locus coeruleus.
• Noradrenaline is released in the locus caeruleus.
• 5-HT is released in the nucleus raphe magnus.
• These areas then communicate with the spinal cord to reduce pain signals.

Peripheral Modulation of Nociception

• TrkA, Nerve Growth Factor (NGF) and potassium channels are involved in modulation.
• Prostanoid receptors, VGNa, VR-1, BK₂ bradykinin, H₁ histamine, opioid/cannabinoid receptor, and morphine/anandamide aid in the process.

Opioid Receptors and Sites of Analgesia

• μ, δ, and κ are opioid receptors.
• μ receptors are involved in supraspinal, spinal, and peripheral analgesia.
• δ receptors are involved in spinal and peripheral analgesia.
• κ receptors are involved in spinal analgesia.

Opioid Receptors and Drugs

• Different opioids bind to the different receptors.
• Morphine binds to μ, δ, and κ receptors.
• Methadone binds to μ receptors.
• Fentanyl binds to μ and κ receptors
• Codeine binds to μ receptors.
• Buprenorphine binds to μ receptors.

Behavioural Responses of Opiate Drugs

• μ receptors induce analgesia, euphoria, respiratory depression, and constipation.
• κ receptors induce analgesia, dysphoria, and diuresis.
• δ receptors induce analgesia.

Behavioural Responses of μ-Opioid Receptor Activation

• Desirable effects include analgesia, euphoria, constipation, sedation, and cough suppression.
• Undesirable effects include respiratory depression, euphoria (depending on dose), constipation, sedation, nausea and vomiting, tolerance, itching, psychological dependence, and physical dependence.

Tolerance

• Tolerance is characterized by requiring higher doses for equivalent effect due to continued drug use.
• This is demonstrated by graphs showing the relationship between morphine dose and effect.

Routes of Administration: Opiates

• Oral (pills), intravenous injection, epidural (fentanyl/pethidine), transdermal patch (fentanyl), lollipop (fentanyl).

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

• These are widely used therapeutic agents, encompassing over 50 available types (e.g., aspirin, ibuprofen, diclofenac, paracetamol).
• Their actions include anti-inflammatory, anti-pyretic, and analgesic effects.
• These effects are related to decreased prostaglandin synthesis.

Disadvantages of NSAIDs

• NSAIDs have multiple side effects due to their involvement in various bodily processes, including gastric irritation, kidney disorders, and potential for overdose (paracetamol).
• Specific COX-2 inhibitors exhibit reduced side effects compared to traditional NSAIDs.

Specific COX-2 Inhibitors

• These, e.g., Rofecoxib (Vioxx) and Celecoxib (Celebrex), selectively target COX-2.
• COX-1 is present throughout the body, impacting wider functions while COX-2 is mainly involved in inflammatory responses.

Neuropathic Pain

• Neuropathic pain arises from peripheral nerve damage, sometimes termed pathological pain.
• It isn't responsive to standard opioid/NSAID pain treatments.

Other Analgesic Approaches

• Other treatments include tricyclic antidepressants (e.g., imipramine), antiepileptic drugs (e.g., gabapentin), cannabinoid receptor agonists, glutamate receptor blockers (e.g., MK801), neurokinin receptor blockers, and nociceptor blockers (e.g., TRPV1, P2X3).

This quiz covers essential concepts related to pain and nociception, as well as the pharmacology of analgesic and opiate drugs. You'll explore the transmission of pain signals, the role of analgesic medications like NSAIDs, and the World Health Organization's pain management guidelines. Test your knowledge of these crucial topics in pain management.