Figure 6.1 |
Most of the sensory and somatosensory modalities are primarily informative, whereas pain is a protective modality. Pain differs from the classical senses (hearing, smell, taste, touch, and vision) because it is both a discriminative sensation and a graded emotional experience associated with actual or potential tissue damage.
Pain is a submodality of somatic sensation. The word "pain" is used to describe a wide range of unpleasant sensory and emotional experiences associated with actual or potential tissue damage. Nature has made sure that pain is a signal we cannot ignore. Pain information is transmitted to the CNS via three major pathways (Figure 6.1).
Most ailments of the body cause pain. The ability to diagnose different diseases depends to a great extent on the knowledge of the different qualities and causes of pain. Sensitivity and reactivity to noxious stimuli are essential to the well-being and survival of an organism. Pain travels through redundant pathways, ensuring to inform the subject: “Get out of this situation immediately.” Without these attributes, the organism has no means to prevent or minimize tissue injury. Individuals congenitally insensitive to pain are easily injured and most of them die at an early age.
For thousands of years, physicians have tried to treat pain without knowing the details of the ways in which pain is signaled from the injured part of the body to the brain, or the ways in which any of their remedies worked. Recent discoveries about how the body detects, transmits and reacts to painful stimuli, have allowed physicians to relieve both acute and chronic pain.
Pain Receptors
Pain is termed nociceptive (nocer – to injure or to hurt in Latin), and nociceptive means sensitive to noxious stimuli. Noxious stimuli are stimuli that elicit tissue damage and activate nociceptors.
Nociceptors are sensory receptors that detect signals from damaged tissue or the threat of damage and indirectly also respond to chemicals released from the damaged tissue. Nociceptors are free (bare) nerve endings found in the skin (Figure 6.2), muscle, joints, bone and viscera. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect damage. The TRP channels are similar to voltage-gated potassium channels or nucleotide-gated channels, having 6 transmembrane domains with a pore between domains 5 and 6. They transduce a variety of noxious stimuli into receptor potentials, which in turn initiate action potential in the pain nerve fibers. This action potential is transmitted to the spinal cord and makes a synaptic connection in lamina I and/or II. The cell bodies of nociceptors are mainly in the dorsal root and trigeminal ganglia. No nociceptors are found inside the CNS.
Figure 6.2 |
Nociceptors are not uniformly sensitive. They fall into several categories, depending on their responses to mechanical, thermal, and/or chemical stimulation liberated by the damage, tumor, and/or inflammation.
Skin Nociceptors. Skin nociceptors may be divided into four categories based on function. The first type is termed high threshold mechanonociceptors or specific nociceptors. These nociceptors respond only to intense mechanical stimulation such as pinching, cutting or stretching. The second type is the thermal nociceptors, which respond to the above stimuli as well as to thermal stimuli. The third type is chemical nociceptors, which respond only to chemical substances (Figure 6.2). A fourth type is known as polymodal nociceptors, which respond to high intensity stimuli such as mechanical, thermal and to chemical substances like the previous three types. A characteristic feature of nociceptors is their tendency to be sensitized by prolonged stimulation, making them respond to other sensations as well.
Joint Nociceptors. The joint capsules and ligaments contain high-threshold mechanoreceptors, polymodal nociceptors, and "silent" nociceptors. Many of the fibers innervating these endings in the joint capsule contain neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP). Liberation of such peptides is believed to play a role in the development of inflammatory arthritis.
Visceral Nociceptors. Visceral organs contain mechanical pressure, temperature, chemical and silent nociceptors. The visceral nociceptors are scattered, with several millimeters between them, and in some organs, there are several centimeters between each nociceptor (Figure 6.3). Many of the visceral nociceptors are silent. The noxious information from visceral organs and skin are carried to the CNS in different pathways (Figures 6.3 and 6.4).
Figure 6.3 |
Figure 6.4 |
Silent Nociceptors. In the skin and deep tissues there are additional nociceptors called "silent" or "sleep" nociceptors. These receptors are normally unresponsive to noxious mechanical stimulation, but become “awakened” (responsive) to mechanical stimulation during inflammation and after tissue injury. One possible explanation of the "awakening" phenomenon is that continuous stimulation from the damaged tissue reduces the threshold of these nociceptors and causes them to begin to respond. This activation of silent nociceptors may contribute to the induction of hyperalgesia, central sensitization, and allodynia (see below). Many visceral nociceptors are silent nociceptors.
Activation of the nociceptor initiates the process by which pain is experienced, (e.g., we touch a hot stove or sustain a cut). These receptors relay information to the CNS about the intensity and location of the painful stimulus.
