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Pain is a vital function of the human body, involving nociceptors and the central nervous system (CNS) to transmit messages from noxious stimuli to the brain. The mechanism for neuropathic pain is distinct as it is caused by injury to the nervous system itself and can occur without the presence of noxious stimuli.
Nociceptors are sensory receptors that are responsible for detecting harmful or noxious stimuli and transmitting electrical signals to the nervous system. The receptors are present in skin, viscera, muscles, joints and meninges to detect a range of stimuli, which may be mechanical, thermal or chemical in nature.
There are two main types of nociceptors:
Additionally, there are silent nociceptors that are usually unresponsive to stimuli but can be “awoken” with high-intensity mechanical stimuli in response to chemical mediators in the body.
Nociceptors may have a variety of voltage-gated channels for transduction that lead to a set of action potentials to initiate the electrical signaling into the nervous system. The excitability and behavior of the cell depend on the types of channels present in the nociceptor.
It is important to distinguish between nociception and pain when considering the mechanism of pain. Nociception is the normal response of the body to noxious stimuli, including reflexes below the suprathreshold that protect the body from harm. Pain is only perceived when superthreshold for the nociceptors to reach an action potential and initiate the pain pathway is reached, which is relatively high.
The nociceptors conduct the electrical signaling message to the dorsal horn of the spinal cord, where a complex array of neurons are involved in the synaptic connections that process nociception and pain. There is not a single pathway that is responsible for the generation of pain in the central nervous system, but a combination of pathways are involved in the propagation of signals to the cerebral cortex.
The perception of pain results from processing of the electrical signals in various regions of the brain. This explains the varied responses and emotional reactions when an individual experiences pain.
The mechanisms that lead to the development of persistent neuropathic pain are more complex than nociceptive pain and should be thought of as distinct.
Neuropathic pain occurs primarily as a result of injury to the nerves involved in the pain pathways in the nervous system, leading to an alteration in the way pain is processed. This usually causes increased pain signal transmission, to the extent that innocuous stimuli may cause a sensation of pain.
Hyperalgesia is a type persistent inflammatory pain that involves increased excitability and nervous response to noxious stimuli, leading to higher sensitivity to pain.
There are also some psychological factors that can influence the experience and extent of pain, known of modulatory influences. These include stress, fear and anxiety and it is widely believed that high levels of these factors can initiate, worsen or prolong episodes of pain in susceptible individuals.