Pathophysiology of Pain

Nature of pain Pain is described as an unpleasant sensation associated with a specific part of the body [1]. It is produced by processes that either damage, or are capable of damaging, the tissues. Such damaging stimuli are called ‘‘noxious’’ and are detected by specific sensory receptors called ‘‘nociceptors’’ [2]. Nociceptors are identified as C-fibers and Ad-fibers. By definition, nociceptors respond selectively to noxious stimuli. These nociceptors are free nerve endings with cell bodies in the dorsal root ganglia and terminate in the superficial layers of the dorsal horn of the spinal cord. Here they relay messages by releasing neurotransmitters such as glutamate [3], substance P, and calcitonin gene related peptide (CGRP) [4,5]. These ‘‘pain’’ neurotransmitters will result in the activation of the second-order neuron via their corresponding receptor. The second-order neuron crosses the spinal cord to the contralateral side and travels up the spinothalamic tract until it reaches the thalamus. From there the third-order neuron is activated, traveling from the thalamus to the somatosensory cortex, which allows for the perception of pain. It should be mentioned that at the level of the spinal cord, secondorder neurons result in the direct activation of lower motor neurons in the ventral horn of the spinal cord, provoking a reflex withdrawal from the noxious stimulus. Likewise, there are interneurons at the level of the spinal cord that will modulate the incoming pain information.