Pain (nociception) is a subjective experience with both sensory and emotional components arising from actual or potential tissue damage. It is frequently a traumatic feature of many diseases and the relief of pain is an important clinical priority. The main pain pathways are shown in Fig. 13.1 . Acute pain is a normal physiological response to an excessively noxious stimulus associated with actual or potential tissue damage. In contrast, chronic pain might elicit hyperalgesia increased pain associated with a mild noxious stimulus), allodynia (pain evoked by a non-noxious stimulus) and spontaneous pain (no stimulus).
Analgesia (The Relief of Pain)
The main pain-relieving drugs are the opioids , which modify both the transmission of pain signals to the brain and the subjective perception of the painful stimulus, but other drugs can be helpful in alleviating some types of pain. Mild/moderate musculoskeletal pain can be alleviated by reducing the nociceptive stimulus through decreasing the formation of chemical mediators in areas of tissue damage ( Fig. 13.1 ). Nonsteroidal anti-inflammatory drugs ( NSAIDs ) treat pain by inhibiting the enzyme cyclooxygenase leading to a reduction in the formation of prostaglandins ( Chapter 16 ). (Note: paracetamol, which similarly inhibits cyclooxygenase, is also widely used for mild pain, but lacks anti-inflammatory action.) Certain types of pain can be controlled by local anaesthetics ( Chapter 27 ) or nitrous oxide inhalation ( Chapter 27 ). The pain of trigeminal neuralgia is susceptible to carbamazepine (an antiepileptic drug) and the pain of migraine to treatment with 5-HT 1 agonists (e.g. sumatriptan ) or ergotamine ( Chapter 12 ). Pain associated with damage to nerves (neuropathic pain) is often resistant to opioids and better treated with tricyclic antidepressants (e.g. amitriptyline) ( Chapter 12 ) or selected antiepileptic drugs (e.g. gabapentin).
There are two categories of opioid drugs:
Morphine and related compounds such as diamorphine (heroin) and codeine.
Synthetic analogues of morphine such as pethidine, fentanyl, methadone , pentazocine and buprenorphine.
Mechanism of action
Opioids act on opioid receptors, of which there are three main types: μ, δ and κ. A fourth receptor, the opioid-receptor-like (ORL) or nociception receptor, is now included in the same family, although it is insensitive to morphine-like drugs and a role in nociception is still uncertain.
Opioid analgesics act as agonists on opioid receptors. Some compounds structurally related to morphine act as partial agonists (nalorphine, levallorphan and buprenorphine) and can also have antagonist activity. Some are full antagonists ( naloxone, naltrexone ); these can inhibit/reverse the action of the agonists and can be used as antidotes in case of opioid overdose.
Many endogenous peptide agonists are essential components of an endogenous analgesia system which underlies the reduced pain sensations that occur under conditions of stress. These include β- endorphin, met-enkephalin, leu-enkephalin, dynorphin and the endomorphins . They are derived from the gene products preproopiomelanocortin, preproenkephalin , and preprodynorphin . Recent work suggests that endomorphins are the normal ligands for the μ-receptor. Table 13.1 gives details of the actions of these various substances on the opioid receptors.