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nociceptors that serve the skin are sensitive to higher intensities of stimuli. Not all tissues have nociceptors (e.g., fat tissues are relatively insensitive to noxious stimuli). However, muscle, periosteum, and especially the interface between ligaments or tendons and bone are richly innervated by nociceptors. Correspondingly, surgical manipulation of fat is relatively painless, whereas manipulation of muscle or bone at tendon insertion sites is painful.

Nociceptors can also assist in healing and may even be involved in neuroimmune mechanisms. When nociceptor innervation to the skin is blocked, there is delay in wound healing, and the thickness of the epidermis is reduced. Neurogenic inflammation is another function of nociceptors; activation of nociceptors prompts a release of potent vasoactive peptides that leads to redness and increased permeability of the vessels.

Signals from nociceptors are transmitted by the peripheral nerve to cells in the spinal cord. Damage to the peripheral nerve (e.g., carpal tunnel syndrome, spinal root compression) may lead to unusual sensations, the sensation of pain, or the loss of sensation (e.g., numbness) in the part of the extremity served by the nerve. The spinal cord is an important processing center for noxious information. Nociceptive inputs have connections to motor neurons in the dorsal horn; this accounts for pain-induced muscle contractions (muscle spasms). Specialized cells in the spinal cord also transmit information from nociceptors to higher brain centers. These inputs to higher centers arouse descending pathways back down the spinal column, which in turn regulate the sensitivity of the nociceptive neurons. Other inputs from peripheral pathways (e.g., touch systems) may interact with the nociceptive inputs to regulate the sensitivity of the cells in the spinal cord. Thus, the sensitivity of the pain-signaling pathways is highly plastic.

Nociceptors that serve different deep tissues have convergent inputs to the spinal cord; these lead to the phenomenon of referred pain. Thus, a person with a heart attack may feel pain in the left arm; a person with a herniated cervical disc feels muscle tenderness in the trapezius muscle, and a person with carpal tunnel syndrome may feel pain in the elbow and upper arm.

Injury may induce changes in pain sensibility. Tissues may become hyperalgesic; that is, the same stimulus produces a greater sensation of pain. Lightly touching the skin may be associated with pain (allodynia). Hyperalgesia results from two forms of sensitization: peripheral and central. Nociceptors (peripheral) themselves become more sensitive to heat and mechanical stimuli, and the spinal cord cells (central) become sensitized as well. As part of this central sensitization, the nerve fibers concerned with touch sensation acquire the capacity to activate the spinal cord cells that serve pain. This accounts for the phenomenon of allodynia,