In detail

Sensory system: pain perception, mechanisms and regulation

Sensory system: pain perception, mechanisms and regulation

Pain is defined as an unpleasant sensory and emotional experience associated with potential or actual tissue damage.

Pain is not just a physical sensation.. It is influenced by attitudes, beliefs, personality and social factors, and can affect emotional and mental well-being.

Although two people may have the same pain condition, your experience of living with pain can be very different: if you live with pain, you would already know.


  • 1 Types of pain
  • 2 The Nociceptors
  • 3 Neurophysiological mechanisms
  • 4 Central regulation of pain perception
  • 5 Physiological basis of pain modulation
  • 6 Modulation of nociceptive transmission

Types of pain

Acute pain: It lasts a short time and occurs after surgery or trauma or another condition. It acts as a warning for the body to seek help. Although it usually improves as the body heals, in some cases, it may not.

Chronic pain: It lasts beyond the expected time for healing after surgery, trauma or another condition. It can also exist without a clear reason at all. Although chronic pain can be a symptom of another disease, it can also be a disease in itself, characterized by changes within the central nervous system.

The Nociceptors

Nociceptors are nerve endings free of sensory neurons with the body in the dorsal root ganglia, and which can be classified as: mechanosensitive, mechanothermal and polymodal nociceptors.

There are few sensory neurons specialized only in the assessment of visceral pain. Many times the pain information from the viscera reaches the SNC through neurons that also carry skin information. Consequently, an internal organ disorder is sometimes perceived as pain in a cutaneous receptor field. The most common clinical example is pain as a result of some type of injury to the heart muscle that is attributed to the upper chest wall, with irritation in the left arm and hand. Pain in a place that is not the real origin is called referred pain.

Neurophysiological mechanisms

Most stimuli that produce damage or inflammation in the tissue release different substances that act on nociceptors:

After tissue damage or inflammation, different substances that act on nociceptors are released sensitizing or exciting them.

  • The prostaglandins, are responsible for sensitizing nociceptors to lower their threshold.
  • The bradykinin or histamine, directly excite nociceptors.
  • The activated nociceptors themselves release substances, such as some peptides, among which substance P is found. Substance P produces the release of histamine which exerts a potent exciting action of the nociceptors.

Surely, you have ever experienced the phenomenon of hyperalgesia. Hyperalgesia is an increase in sensitivity and response to stimulation of the area surrounding damaged tissue.. Thus, in the tissue that is around the lesion, the stimuli that normally would not produce pain, are perceived as painful and the stimuli that would normally be painful, are even more so. The cause of this phenomenon is the sensitization of nociceptors by different substances released after tissue injury. The release of bradykinin, histamine, prostaglandins and other agents increases the responsiveness of nociceptive terminations.

This chemical signaling is a protection mechanism of the injured area, as it relates to the promotion of healing and protection against infections.

The participation of these substances has been used in the production of analgesics. For example, aspirin acts by inhibiting cyclooxygenase, an important enzyme in the biosynthesis of prostaglandins.

Central regulation of pain perception

There is not always a clear correspondence between the objective reality of a painful stimulus and the subjective response it evokes..

During World War II, Henry Beecher and his collaborators observed that American soldiers wounded in World War II returning from battle, said they felt no pain from the wounds and did not even need medication. It seems that his perception of pain was diminished by the comfort of having survived the war.

These observations show that environmental facts can decrease pain and together with the placebo effect they make it clear that the perception of pain is subject to a central modulation.

The Placebo effect It is defined as a physiological response after the administration of a pharmacologically inert remedy.

It has been found that up to three out of four patients who suffer pain in a postoperative wound feel relief after a saline injection instead of an analgesic.

Physiological basis of pain modulation

Multi-core Brain stem tracks that reach the marrow and control the transmission of pain. The electrical or pharmacological stimulation of these nuclei has analgesic effects.

  • The origin of these pathways is the gray periacueductal substance (SGP) of the midbrain and the superior protuberance. This nucleus receives projections from the spinoreticular division of the anterolateral system, the hypothalamus, thalamus and the cerebral cortex.
  • From the GSP, descending routes leave until the rafe magnocellular nucleus (NMR) and nuclei of the spinal bulb ventral rostral (such as the paragigantocellular reticular nucleus, NRPG). The latter also receives projections from the noradrenergic groups of the bulb and the bump.
  • The fibers that start from NRPG and NMR reach the spinal cord where they establish synaptic contacts and influence nociceptive afferent neurons.

Stimulation of these nuclei inhibits the transmission of nociceptive information from the spinal cord.

Modulation of nociceptive transmission

The analgesic effects are basically related to the endogenous opioid release.

The opium analgesic effects they have known each other since ancient times, but until the beginning of the 19th century their active principle was not isolated, the morphine.

The administration of small doses of opiates in certain areas of the brain has a potent analgesic effect. But this effect is more effective when the administration is performed in areas where its stimulation also produces analgesia, such as the GSP and the faceventral region of the bulb.

To know the role of opiates in pain modulation is essential:

  • The location of opioid receptors in the SN
  • The discovery of endogenous opioid substances

The distribution of peptides and opioid receptors extends throughout the SNC, coinciding with the neural circuits involved in the production of analgesia.

Opioid peptides (enkephalins Y dinorphins) are located in areas involved in the processing or modulation of pain.

Neurons that contain these peptides are located at:

  • The GSP.
  • Bulb faceventral zone
  • Spinal Cord Dorsal Horn

So, there is a coincidence between the areas where the endogenous opioids are found and the areas that stimulate produce analgesic effects. Therefore, it seems clear that these areas must participate in the descending mechanisms of pain control.

The endogenous opiates, released by environmental stimulation or when administered as a drug, stimulate opioid receptors of SGP neurons. These opioid receptors are found in inhibitory interneurons. As the effects of opiates appear to be inhibitory, their administration inhibits inhibitory interneurons causing an activation of the neurons on which these interneurons synapt.

Neural circuit involved in opioid analgesia.

In the marrow neurons from NRPG also arrive. These neurons release norepinephrine on interneurons that inhibit projection neurons that reach the thalamus. This route does not act through the opiates and, therefore, analgesia is the result of the action of different mechanisms and circuits.

The fact that the body has these pain modulating systems, has raised the study of what are the situations that activate them.

It seems that these systems would be activated during the conduct of biologically important behaviors such as fighting or mating. For example, males struggling to access females during the mating season would not transmit their genes if the pain caused by the wounds caused withdrawal responses that interfered with the fight. Conditions like this make the pain decrease.

It has been discovered that pain can be inhibited in situations of stress: stress-induced analgesia. For example, exposure to an inescapable electric shock raises the pain threshold. This effect can be partially blocked by the administration of naloxone.

As we have already mentioned, pain can be reduced, in some people, with the administration of a placebo. When some people take medication that they believe will reduce pain, the release of endogenous opiates is activated. This effect is eliminated with the administration of naloxone (opioid receptor blocker). Thus, for some people, a placebo is not "pharmacologically inert." The placebo effect is probably intervened by the connections from the prefrontal cortex in the GSP.

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