Pain

·        Pain and drugs.

·        Phenomenon of pain.

·        Mechanism of analgesia.

Pain and Drugs

1.    Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

2.       Analgesic drug: a drug that relieves pain due to multiple causes.

3.       Classification:

a.       Narcotic: act on the CNS and cause drowsiness.

b.    Non-narcotic: act chiefly peripherally.

4.       Adjuvant drugs:

a.    Used alongside analgesics in the management of pain.

b.    They are not themselves analgesics.

c.    May modify the perception or the concomitants of pain that make it worse.

5.       Principles of management:

a.       Acute pain: managed primarily by analgesic drugs.

b.       Chronic pain: often requires adjuvant drugs in addition as well as nondrug measures.

Phenomenon of Pain

1.    Pain can occur without tissue injury or evident disease and can persist after injury has healed.

2.       Emotion (anxiety, fear, depression) is an inseparable concomitant of pain and can modify both it’s intensity and the victim’s behavioral response.

3.       Nociception:

a.    A consequence of tissue injury (trauma, inflammation) causing the release of chemical mediators which active nociceptors in the tissue.

b.       Nociceptors are specialized nerve endings serving their own afferent fibres (A-delta and C).

4.    Pain sensation:

a.    A result of nociceptive input plus a pattern of impulses of different frequency and intensity from other peripheral receptors.

b.       These are processed in the brain whence modulating inhibitory impulses pass down to regulate the continuing afferent input.

c.    But pain can occur without nociception (some neuralgias) and nociception does not invariably cause pain.

d.    Pain is a psychological state though most pain has an immediately antecedent physical cause.

5.       Suffering:

a.    A consequence of pain and of lack of understanding of patients of the meaning of pain.

b.       Comprises anxiety and fear and depression which will be affected by patients’ personalities, and their beliefs about the significance of the pain.

c.       Depression makes a major contribution to suffering; it is treatable, as are the other affective concomitants of pain.

6.    Pain behavior:

a.       Behavior that is interpreted by others as signifying pain in the victim, e.g. facial expression, restlessness, medicine-taking.

b.    In chronic pain: development of querulousness, depression, despair and social withdrawal.

7.       Acute pain:

a.       Transmitted by fast conducting A-delta fibers with major nociceptive input.

b.    Seen by patients as a transient sometimes severe threat.

c.    May be dealt with effectively with drugs, by infection if necessary.

8.       Chronic pain:

a.       Transmitted by slow conducting type C fibres.

b.       Presents a depressing future to the victim who sees no prospect of release from suffering.

c.       Analgesics alone are often insufficient and adjuvant drugs as well as nondrug therapy gain increasing importance.

d.       Continuous use of these drugs is best avoided in chronic pain, except that of palliative care.

e.       Sedation should be avoided and therapy should be oral if possible.

f.       Antidepressants can often be useful.

Mechanisms of Analgesia

1.       Endogenous opioid neurotransmitters:

a.    They are: endorphins, dynorphins and enkephalins.

b.    They are found in the spinal cord and brain.

c.       Constitute a pain inhibitory system that is activated by nociceptive and other input.

d.       Administered opioids produce analgesia via the specific opioid receptors of this system.

2.       NSAIDs:

a.       When a tissue is injured, prostaglandins synthesis in that tissue increases.

b.       Prostaglandins sensitize nerve endings, lowering their threshold of response to stimuli, mechanical and chemical, allowing the other mediators of inflammation, e.g. histamine, serotonin, to intensify the activation of the sensory endings.

c.       NSAIDs prevent the synthesis of prostaglandins by inhibiting the enzyme prostaglandin G/H synthase and are hence effective in relieving pain due to inflammation of any kind.

d.       Analgesic and anti-inflammatory effects are not parallel: aspirin relieves pain rapidly at doses that do not reduce inflammation.

3.       Corticosteroids:

a.       Diminish inflammation of all kinds by preventing prostaglandin synthesis via inhibiting phospholipase A2, the enzyme which releases arachidonic acid, the precursor of prostaglandins from the cell membrane.

b.       Short-term use may be valuable; longterm use poses many problems.

c.    In general corticosteroids should be withdrawn after one week if there is no benefit.

4.    The pain threshold is lowered by anxiety, fear, depression, anger, sadness, fatigue or insomnia and is raised by relief of these and by successful relief of pain.

Choice of Analgesics

1.    Mild pain: non-narcotic analgesics or NSAIDs, e.g. aspirin, ibuprofen, paracetamol.

2.       Moderate pain:

a.       Narcotic analgesics, low-efficacy opioids: codeine, pentazocine.

b.       Combined therapy of NSAIDs + low-efficacy opioid.

3.       Severe pain:

a.       High-efficacy opioids: morphine, pethidine, buprenorphine.

b.    An added NSAID is useful is there is a substantial tissue injury component, e.g. gout, bone metastasis.

4.       Overwhelming acute pain:

a.    High efficacy opioid + a sedative / anxiolytic.

b.    Or a phenothiazine tranquilizer, e.g. chlorpromazine.

5.       Using two analgesics:

a.    Two drugs of the same class / mechanism of action are unlikely to benefit unless there is a difference in emphasis.

b.    A low-efficacy opioid can reduce the effectiveness of a high-efficacy opioid by successfully competing with the latter for receptors.

c.       Partial agonist opioids will also antagonize the action of other opioids and may even induce the withdrawal syndrome in dependent subjects.