Paracetemol
This is a simple analgesic that can be beneficial for mild pain. Widely available and safe within prescribed doseages, paracetemol probably works by indirectly inhibiting enzymes known as cyclooxygenases (COX-1 & COX-2). In addition to analgesic effects, there is the well-known antipyretic action (reduces temperature).
NSAIDs (Non-steroidal anti-inflammatory drugs), e.g. neurofen, ibuprofen, diclofenac
Commonly prescribed for inflammatory pain, NSAIDs are active in the inhibition of the COX exnzymes. This has been demonstrated scientifically with both COX-1 and COX-2 enzymes although many anti-inflammatories are not able to be selective and hence inhibit both. This is the reason for the well-documented side-effects such as gastric irritation and renal failure. Your doctor will advise you on the use of these drugs according to your current medical condition.
COX-1 is expressed constitutvely and gives rise to prostaglandins which have a a role in normal cell function. COX-2 is expressed when an inflammatory process is underway to produce more prostanoids. Inhibiting the prostaglandin activity by the use of NSAIDs means that normal physiology is affected and therefore the adverse effects can be experienced.
Prostaglandins are metabolised from arachidonic acid by the COX enzymes following tissue damage. NSAIDs act by inhibiting these enzymes and therefore inhibit prostaglandin production. Prostaglandins have the ability to sensitise nerve endings by altering the membrane excitability, therefore the nerve becomes more likely to send 'danger' signals to the spinal cord. There are other breakdown products that have this action, but prostaglandins are one of the best understood. Following sensitisation, pripheral nerves become more respondant to mechanical, chemical and thermal stimuli, hence the reason for pain when we press on or near injured tissue (mechanical), why it is painful to take a shower with sunburn (temperature) and why exercise can be painful (release of acids, i.e. chemical).
Opioids (e.g. morphine, tramadol, codeine, dihydrocodeine, pethidine)
Opioids have been studied in detail over the last 30 years and now we have a great deal of knowledge about how they work and how they affect the nervous system. The discovery of the opioid receptor (like a lock that a specific key would fit, the key being the opiate drug and the lock being the receptor) and where these receptors are situtated. Knowing that there are receptors in the brain for example, means that we can explain the feelings of drowsiness and cognitive impairment (ability to concentrate).
Once an opiate has bound upon a receptor, it inhibits several channels that cross the nerve membrane (calcium and potassium) because it is linked to these channels. The channels allow for the passing of specific ions which alter the excitability of the nerve (i.e. become more excited and sensitive with a change in the balance of flow of these ions). There are further effects within the cell that reduce excitability of the nerve (inhibition of several pathways of activity that lead to increased excitability; cAMP & MAP kinase cascades).
Anticonvulsants (e.g. carbamazepine, gabapentin, pregabalin)
Anticonvulsants are used to treat neuropathic pain (see page on pain types) that is underpinned by changes in nerve excitability. This is as a result of an alteration in the channel (sodium & calcium) expression upon the nerve membrane (see opioids for brief explanation of channels) that is similar to changes that occur in epilepsy (this does not mean that you have epilepsy just because there are some similarities in channel changes).
Gabapentin decreases the on going firing of signals that are generated through sodium channel activity, inhibits calcium channels and acts with the NMDA receptor. The end result is reduced excitability and less signalling to the spinal cord from the periphery.
Carbamazepine is related to tricyclic antidepressants. It inhibits noradrenaline and has an effect upon sodium channels therefore has inhibitory effects by reducing spontaneous nerve activity (a feature of neuropathic pain) and promoting descending inhibition (signals descend from higher levels, brain & brain stem, to inhibit ascending danger signals).
Pregabalin has a similar action to gabapentin. It has been shown to be effective in diabetic neuropathy and postherpetic neuralgia.
Antidepressants (e.g. tricyclics, SSRIs; amitriptyline, fluoxetine, citalopram, paroxetine)
Antidepressants have been discovered to provide pain relief by activating the descending pain-inhibiting system (brain stem to spinal cord). This includes an endorphin release link between the periaqueductal gray (PAG) and the raphe nucleus and a serotonergic link between the raphe nucleus and the dorsal horn of the spinal cord. There is also a noradrenaline pathway from the locus coeruleus to the spinal cord. The most effective drugs appear to be those that have a combined effect upon both the serotonergic and noradrenaline pathways.
Antidepressants are effective in the treatment of neuropathic pain, relieving the stabbing and steady pains. There are side-effects that can be experienced. Your doctor should tell you about the dosage and how the drug is best taken.
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