Pain signaling

Regional anesthesia is the injection of a local anesthetic around nerves so that the area supplied by these nerves will not send pain signals to the brain. The anesthetized area is usually larger than the area affected by... 

But potassium nitrate is also used in toothpastes that are formulated to make teeth less sensitive to pain. As gums recede and the tooth root dentin becomes exposed, teeth can become hypersensitive to hot or cold foods. Potassium nitrate interferes with the transmission of pain signals in the nerves of the teeth. 

The mechanisms of pain and the ability to control pain may vary in different pain states. This is of particular importance in consideration of a rational basis for the treatment of both inflammatory and neuropathic pain where the damage to tissue and nerve leads to alterations in both the peripheral and central mechanisms of pain signalling. In respect of existing drug therapies, this plasticity, the ability of the system to change in the face of a particular pain syndrome, explains the effectiveness of NSAIDs in inflammatory conditions and yet is also responsible for some of the limitations in the effectiveness of opioids in neuropathic pain. 

The mechanism of action of these anesthetics involves the blockade of sodium channels in the membrane of the second-order sensory neuron. The binding site for these anesthetics is on a subunit of the sodium channel located near the internal surface of the cell membrane. Therefore, the agent must enter the neuron in order to block the sodium channel effectively. Without the influx of sodium, neurons cannot depolarize and generate an action potential, so the second-order sensory neuron cannot be stimulated by impulses elicited by pain receptors associated with the first-order sensory neuron. In other words, the pain signal is effectively interrupted at the level of the spinal cord and does not travel any higher in the CNS. In this way, the brain does not perceive pain. 

Signals are also transmitted to the reticular formation of the brainstem by way of the spinoreticular tract. The reticular formation plays an important role in the response to pain. First, it facilitates avoidance reflexes at all levels of the spinal cord and, second, it is responsible for the significant arousal effects of pain. Signals from the reticular formation cause an increase in the electrical activity of the cerebral cortex associated with increased alertness. Furthermore, it sends nerve impulses to the hypothalamus to influence its functions associated with sudden alertness, such as increased heart rate and... 

Figure 8.1 The pain pathway. The pain signal is transmitted to several regions of the brain, including the thalamus reticular formation hypothalamus limbic system and somatosensory cortex. Each region carries out a specific aspect of the response to pain.

The cell bodies of third-order sensory neurons are located in the thalamus. These neurons transmit the pain signal to the somatosensory cortex. The function of this region of the brain is to localize and perceive the intensity of the painful stimulus. Further transmission of the signal to the association areas of the cerebral cortex is important for the perception and meaningfulness of the painful stimulus. 

Figure 8.2 The endogenous analgesic system. The three major components of the endogenous analgesic system include the periaqueductal gray matter in the midbrain nucleus raphe magnus in the medulla and pain inhibitory complex in the dorsal horns of the spinal cord. This system causes presynaptic inhibition of pain fibers entering the spinal cord. The binding of enkephalin to opioid receptors on the pain fibers prevents release of the neurotransmitter, substance P. As a result, the pain signal is terminated in the spinal cord and does not ascend to higher centers in the CNS.

Morphine may be administered orally, intravenously, or epidurally. An advantage of epidural administration is that it provides effective analgesia while minimizing the central depressant effects associated with systemic administration. The mechanism of action with the epidural route of administration involves opioid receptors on the cell bodies of first-order sensory neurons in the dorsal root ganglia as well as their axon terminals in the dorsal hom. Stimulation of these receptors inhibits release of substance P and interrupts transmission of the pain signal to the second-order sensory neuron. 

May staid with an around-the-clock regimen and switch to prn if/when the painful signal subsides or is episodic. 

What is a synapse In the brain, the nerve cells or neurons are connected at special functional junctions called synapses, which depend on many proteins, including large complexes. They participate in basic functions with important roles in coordinating every characteristic of the nervous system, including physiology, emotions, learning, sleep, memory, and pain signal transmission. 

The pain is mediated via pain receptors (nociceptors) from the damaged tissue. The pain signal... 

The pain signal occurs in the nervous system due to damage or mis-function in the nerve itself... 

Pain without obvious or suspect damage or disease, possibly with weak strengthening of peripheral pain signalling after a healed damage... 

Zieglgclnsberger W, Tolle TR (1993) The pharmacology of pain signalling. Cmr Opin Neu-robiol 3 611-618... 

Other actions of kinins include activation of clotting factors simultaneously with the production of bradykinin. In the kidney, bradykinin production results in an increase in renal papillary blood flow, with a secondary inhibition of sodium reabsorption in the distal tubule. In the peripheral nervous system, bradykinin is important for the initiation of pain signals. It is also associated with the edema, erythema, and fever of inflammation. 

Mectianism of Action An antiadrenergic, sympatholytic agent that prevents pain signal transmission to the brain and produces analgesia at pre- and post-alpha-adrenergic receptors in the spinal cord. Therapeutic Effect Reduces peripheral resistance decreases BP and heart rate. 

There are three principal classes of opiate receptors, designated x, K, and 5, and there exist a number of drugs that are specific for each of these receptor types. However, most of the clinically used opiates are quite selective for the preceptor the endogenous opiates enkephalin, endorphin and dynorphin are selective for the p and 5, 5 and k receptors respectively. When activated by opioids these receptors produce biochemical signals that block neurotransmitter release from nerve terminals, a process that underlies their blockade of pain signaling pathways as well as other effects, such as constipation, diuresis, euphoria, and feeding. 

Codeine also activates pain-control circuits that descend from the section of the brain called the midbrain to the spinal cord, causing the release of naturally produced opioids called endorphins and enkephalins. The endorphins and enkaphalins bind to and activate receptors on cells in the spinal cord that prevent the transmission of pain signals. As discussed in Chapter 3, endorphins and enkephalins are your body s natural chemicals that allow you to feel no pain. ... 

It is important to note that the binding of morphine to opioid receptors in the brain and spinal cord produces the sensation of pain relief it does not attack or eliminate physical causes of pain due to trauma or other injury. At the cellular and molecular level, the binding of opioids with opioid receptors sets off a cascade of events that modulate the release of neurotransmitters involved in pain signaling. 

Although chronic types of pain may generally appear to have no purpose, acute pain acts as an important warning mechanism to the person by instructing the brain to remove the individual from that particular pain stimulus. If for example a person lifts a hot object, pain signals to the brain to put the object down to avoid severe burns. 

Unlike most receptors, nociceptors can become increasingly sensitive after injury (i.e. when the stimulus is very strong) or when the stimulus is continuing or repeated. This sensitization means that there can be a reduction in the threshold for activation (i.e. pain signals will be transmitted in response to even gentle stimuli), an increase in the response to a given stimulus, or even the appearance of spontaneous activity. 

Activation of K+ channels, inactivation of Ca2+ channels and direct inhibition of neurotransmitter release are powerful mechanisms by which opioids inhibit the neuronal transmission of the pain signal. 

---