[Analgesics].

Increased pain fibre activity in response to tissue injury results in changes in gene expression, and prolonged changes in nerves and their environment. The resulting hyperalgesia and prolonged spontaneous pain are due both to increased sensitivity of peripheral nociceptors (primary hyperalgesia) and to facilitated spinal cord transmission (secondary hyperalgesia, receptive field expansion and allodynia). Hyperexcitability of dorsal horn neurones is first triggered by increased neuronal barrage into the central nervous system ('wind-up'), and later by retrograde chemical influences from the peripheral inflammation (central sensitisation). Central transmission and hyperexcitability are mediated by excitatory amino acids (aspartate and glutamate) and by tachykinins (substance P). Normally, the net effect of the activity in a complex network of inhibitory neurones in the spinal cord ('gate control'), driven by descending projections from brain stem sites, is to dampen and counteract the spinal cord hyperexcitability produced by tissue or nerve injury. Thus, peripherally evoked pain impulses pass through a filtering process involving gamma-aminobutyric acid, glycine and enkephalins. The activity of these substances in the spinal cord usually attenuates and limits the duration of pain. In the case of persistent pain, there is evidence of pathological reduction of the supraspinal net inhibitory actions in combination with ectopic afferent input in damaged nerves. Hence, the pathology of chronic pain (neuropathic pain) differs from that of nociceptive pain, and conventional pharmacological treatment of chronic central pain is usually less successful than treatment of inflammation-related pain. The many newly discovered mechanisms for the transmission and modulation of pain impulses are characterised by complex activity-dependent plasticity, which means that therapeutic strategies for persistent pain must be adapted to changing targets--either at the site of injury or at other sites in the central nervous system.

Analgesics↗

PubMed1997

Drug treatment of migraine: Part I. Acute therapy and drug-rebound headache.

Most migraine patients need only abortive treatment for their headaches. By the time they present to a physician, they have already tried many over-the-counter medications for headache relief. Prioritizing treatment according to headache severity and associated symptoms will help the physician determine the most appropriate medications to use. Narcotics should be reserved for use only in patients unresponsive to adequate trials of non-narcotic agents. In some patients, the recurrent nausea and vomiting can be as disabling as the pain; antiemetic agents are an important adjunct to analgesic therapy in these patients. Sumatriptan and dihydroergotamine are more expensive than other migraine agents but have distinct therapeutic advantages in patients with moderate to severe headaches. Some patients experience rebound headache from overuse of analgesics and other headache medications. Educating patients about self-help measures and avoidance of triggers is an important element in the effective management of migraine headaches.

Analgesics↗