MODULATION

• The process by which the nervous system modifies the nociceptor activity is called modulation. The modulatory network is quite different from sensory system and involves a number of brainstem regions (periaquenductal grey and immediately adjacent midbrain, periventricular grey of hypothalamus, the lateral and dorsolateral pontine tegmentum and rostro ventral medulla). Stimulation of any of these sites reduce pains and inhibit nociceptive neurones. Both nor adrenergic and serotonerigc systems are involved. In addition these produce endogenous opiod peptides which are at least partially responsible for analgesia.
• This modulatory system project to the spinal cord along the dorsolateral funiculus. It doesn't work when there is no pain. In summary, pain involves a complex interaction. Modification occurs at the spinal cord with interneurone and descending modulatory network. Transmission to higher levels occur through spino thalamic and reticulo thalamic tract to SSC and limbic system and frontal lobe. The sense of pain is the net result of all these.

PERCEPTION

• When the nociceptive information arrives to the cortex, he takes place the perception of the pain and a complex neuron interaction begins with the superior centers of the brain.
• In this point it begins the suffering and the behavior of the pain.

SUFFERING

• He refers to the way in that the human being reacts to the perception of the pain.
• When the pain is perceived by the cortex, a very complex interaction of many factors begins. 
• Factors like the previous experiences or the borrowed attention to the lesion, they determine until grade the individual will suffer.

• Neural impulses thus produced are carried along the peripheral nerves, nerve roots, spinal cord, brainstem, thalamus and the cortex that ultimately leads to an awareness of pain.
• The majority of primary afferents project to the spinal cord through dorsal root. At the ventrolateral aspect of the dorsal root A-delta and C fibers segregate and enter the spinal cord. Some may project to the spinal cord through ventral root.
• Recent studies suggest, they loop back and enter along the dorsal root. In the spinal cord, the fibers become part of Lissaur's tract which is located at the dorsolateral edge of the spinal cord and divide into ascending and descending branches that extend for one or two spinal segments.
• Spinal cord grey matter is organized into ten laminae (REX) C-fibers project mainly to I and II laminae and A-delta to I to V. The neurons in the cord can be divided into projection neurons (relay to higher centers), excitatory neurons (relay to projection and other interneurons or to motor neuron that mediate spinal reflexes) and inhibitory interneurons (contribute to the control of nociceptive transmission). Laminae I, V, VII, VIII are the major sources of rostaraly projecting nociceptor neuron. Laminae II (substantia gelatinosa) make predominantly local connection that result in important changes in the neuronal activity.
• Among Nocicecptive Transmitters involved in the cord, substance P is well known and found in dense concentration in laminae I and II and in many dorsal root ganglion cells. Other substances are somatostatin, vasoactive intestinal polypeptide, glutamate, aspartate and adenosine triphosphate.
• Gate Control Hypothesis suggests interaction between myelinated and nonmyelinated neurons occurs at inhibitory interneurons in substantia gelatinosa and at dorsal horn. The myelinated afferents said to excite inhibitory interneurons and inhibit pain. The nonmyelinated nociceptors inhibit the inhibitory interneurons. The perceived intensity is the net effect. Although current evidence suggest that it is incorrect, transcutaneous electrical-neuron stimulator (TENS) is developed on this. The major spinal pathways for pain travels in the anterolateral spinal quadrant to the thalamus (spinothalamic tract) and crosses over to the other side 2 or 3 segments above. Certain proportion of pain impulses can be carried in ipsilateral pathway.
• The Spino Thalamic Tract divides into:
  • Lateral division which terminates in posterior nuclear group and ventrobasal nuclei (VPM & VPC). The major projection is from I & V laminae with receptive field restricted to one side of the body usually part of a limb
  • Medial division is called paleo spinothalamic tract and terminate in the central lateral nucleus. The major projection is from entire body surface.
  • Spino reticular projection appear to involve V,VI VII & VIII laminae and have complex receptive fields from both sides similar to paleo spino thalamic tract.
• Thalamic Nuclei project to somoto sensory of cortex (lateral spino thalamic tract) and limbic and frontal lobes (medial and reticulo thalamic). SSC (somato-sensory cortex) is involved in to localization and identification. Limbic system and frontal lobe responsible for emotional aspects suffering and anxiety.