Strategies in the pharmacological management of pain

Analgesics may reduce nocciception and pain by:

• Acting at the site of injury - decrease nociceptor sensitization in inflammation primarily by blocking synthesis of prostaglandins (e.g. NSAIDs)
• Suppressing nerve conduction by blocking/inactivating voltage-activated sodium channels e.g. local anaesthetics, such as lidocaine (aka lignocaine)
• Suppressing synaptic transmission of nociceptive signals in the dorsal horn of the signal cord (e.g. opioids and some anti-depressant drugs)
• Activating (or potentiating) descending inhibitory controls (e.g. opioids, select tricyclic antidepressants)
• Targeting ion channels upregulated in nerve damage (e.g. antiepileptics of several types such as GABA pentinoids)

The WHO analgesic ladder

Analgesics are placed on 'rungs' accordig to their clinical efficacy:

• Strong opioid (e.g. morphine, oxycodone, hydromorphone, heroin, fentanyl)
• Weak opioid (e.g. codeine, tramadol, dextropropoxyphene)
• NSAIDs (e.g. aspirin, diclofenac, ibuprofen, indometacin, naproxen)
• Paracetamol (which is not regarded as an NSAID)
• Combinations of 1+2, or 1+3, are often used in moderate/ severe pain

Regulation of pain - efferent (supraspinal antinociception)

Supraspinal anti-nociception is mediated by descending pathways from brainstem

• Brain regions involved in pain perception and emotion (e.g. cortex, amygdala, thalamus, hypothalamus) project to specific brainstem nuclei
• Neurones of brainstem nuclei give rise to efferent pathways that project to the spinal cord to modify afferent input
• Important brainstem regions include:
  • The periaqueductal grey (midbrain)
  • Locus ceruleus (pons)
  • Nucleus raphe magnus (medulla)