The sensation of pain is a complex biochemical process. Some understanding of the process is important in order to effect an appropriate treatment, as a therapy may be directed at a specific part of the pathway (See Figure 1.)
Pain sensation initiates at the tissue level through specialized nerve fibers called nociceptors. These fibers transduce an electrical signal from a thermal, mechanical, or chemical stimulus. The signal is propagated through the peripheral nerve, the spinal cord (via the spinothalamic tract), and then interpreted by the brain.
Nociceptors are found in the body, especially in the skin, periosteum, arterial walls, teeth, joint surfaces, and falx and tentorium of the cranial vault. There are 2 general types of nociceptors: C (chemical) polymodal receptors, and A-delta polymodal receptors. C-type receptors account for about 80% of nociceptors, and they react to thermal, chemical, and mechanical signals. A-delta-type receptors are activated primarily by thermal and mechanical stimuli. A-delta-type nociceptors are myelinated, and thus they propagate a signal more quickly and are associated with the immediate, “sharp” sensation of pain. In contrast, C-type nociceptors carry a slower signal, associated with delayed, “aching” pain.
Tissue damage releases various chemicals, including leukotrienes, bradykinins, serotonin, histamine, and thromboxanes, which activate C-type nociceptors. Prostaglandins do not directly activate receptors; however, they act as a local mediator that enhances the sensitivity of the free nerve endings and produce pain and edema by their vasodilatory effect. Nociceptors propagate their impulses through the peripheral nerve to their cell body in the dorsal horn of the spinal cord where substance P (a neurotransmitter) is released, which then relays the signal to the cortex via higher-order neurons and the spinothalamic tract.
Inhibition of this pathway is achieved physiologically by several means. First, competitive inhibition by a stronger signal (primarily A-beta fibers) displace the signal from the weaker A-delta and C-type fibers (pain sensation is decreased by rubbing a site of injury). Additionally, endogenous chemicals (endorphins, enkephalins, dynorphins) activate opioid receptors and provide an analgesic effect.
In contrast to somatic pain, which is activated by direct mechanical, thermal, or chemical signals, visceral pain is initiated by ischemia, distention, spasm, or chemical stimulation. The painful sensation is often a result of sensation in the surrounding structure (eg, the liver capsule, as the liver itself is relatively insensitive to pain); thus, localization may be difficult to elicit.
Inadequate treatment of acute pain may result in additional complications including tachycardia, hypertension, and increased myocardial demand that may lead to ischemia; sympathetic stimulation of the digestive tract, leading to decreased motility; suppression of endocrine and immune responses; and the development of chronic pain.12