Opioids In Pain Therapy

摘要

I. Transmission of pain Pain is transmitted via pathways which ascend from the periphery to the central nervous processing areas in the brain. There are different inhibiting control mechanisms on various levels of these ascending pathways but there is no defined morphologic area for processing the perception of pain [1] .The original physical or chemical pain trigger is perceived by specialized receptors. Generated action potentials are sent to the dorsal horns by A(- and C-fibers . The frequency of these are proportional to the intensity of the original trigger. The dorsal horn contains a complex circuitry of neurons that permits not only reception and transmission of nociceptive input but also a high degree of sensory processing . It is subdivided into six laminae where the lamina I is the most dorsal one. Before the nociceptive fibers end in the laminae I and II (substantia gelatinosa) they usually ascend or descend one or two segments. When the nociceptive information has been transmitted through interneurons to the neurons of the lamina V, long axons in the anterolateral tract will transmit it to the higher integrating centers. Usually the 1st neuron of this pathway is located in the spinal ganglia or the ganglia of the cranial nerves. The 2nd neuron is located in the dorsal horn or the rhombencephalon .The synaptic transmitters of sensoric afferent transmission are neuropeptides like Substance P. After synaptic processing in the dorsal horns the nociceptive information together with the peripherally perceived information about temperature is channeled to the contralateral ascending tracts. In contrast propioceptive information is transmitted via the ipsilateral dorsal ascending tracts to the thalmo-cortical system.Depending on the intensity of the incoming nociceptive information there is direct activation of specific flexor and extensor motor neurons via interneurons. The direct activation of autonomic sympathetic neurons by the processing of nociceptive information on the segmental spinal level can lead to immediate changes in the perfusion of defined areas. Referred pain (phenomena of Head`s Zones) can be explained by interneuronal processing on a spinal level where there is a summation of different incoming signals at the first neuronal ganglion in the dorsal horn. By the way of convergent processing in neurons which receive visceral and peripheral information, nociceptive signals below threshold for localized pain perception may cause referred pain. This is only one example of the complex processing of nociceptive signals through the neuronal circuitry in the dorsal horn of the spinal cord .On the spinal level nociceptive sensory input can be modulated not only by the phenomena of central convergence and summation but also through excitatory and inhibitory influences coming from the periphery, local interneurons, the brainstem and the cortex. So afferent signals from C-fibers are usually modulated by inhibitory signals transmitted via A(- and A(-fibers. Descending non-nociceptive pathways also influence the further processing by the localized secretion of enkephalins (6(. This phenomena of segmental inhibition for example is the basis for many alternative treatment regimens as acupuncture or acupressure, since there is a significant modulation of pain perception by activation of related afferent sensory fibers. I.1. Opioid Receptors The different pharmacological action of morphine and the other natural and synthetic opioids led to the assumption that there is a heterogeneous group of opioid receptors which was proven by Martin in 1976. Depending on the classification three to five major receptor subtypes are recognized today, but a further extension and subdivision of receptor subtypes is ongoing.Opioid receptors exist throughout the CNS, with particular high concentrations in the periaqueductal gray area and the dorsal horn of the spinal cord. The greatest abundance of opioid receptors is in the substantia gelatino