The Raw Anatomy of Pain

This is a summary of pain centers which will help you in reading other articles.

We apologize that we have not been able to obtain permission from artists or text publishers to provide a rendering of brain anatomy to accompany this article. However, reprints of Gray’s Anatomy show the entire body and are usually available for less than fifteen dollars at almost any bookstore of size, including Barnes and Noble and Borders. For about $40 has several decent textbooks of brain anatomy. There are sites on the internet, including (Google brain anatomy and you will get images) providing the essential information, so it is not necessary to spend any money.

The real action is in the chemistry now, and not the anatomy anyway, so we recommend you save your money for the time when a good book on pain chemistry comes out. Even experts prefer to study chemoarchitecture, which is beginning to outweigh anatomy as the understanding evolves that traditional named structures are so hopelessly complex that only an understanding of chemical pathways makes any sense. Some parts of the brain may have formed because it was embryologically convenient to do so, but the components do not necessarily all work hand in hand in the same structure. It is necessary to get much smaller, much finer, down to the molecular level, to understand what is going on. Because central pain is a molecular disorder, gross antomy of the brain is only minimally helpful. Steriade’s book on the thalamus is out of print, so you may wish to look at Sherman and Guillery, but even so, it is the neurochemistry which matters, so you probably don’t have to spend money.

Pain has traditionally been spoken of as consisting of first, second, and third order neurons.

1st Order: This neuron goes from the target organ, usually the skin to the dorsal spinal cord. NOCICEPTION. or detection of painful stimulus normally occurs here. Opiate receptors, Nitric oxide, nociceptin and nocistatin operate here.

2nd Order: From the dorsal horn of the spinal cord, this neuron crosses over in front of the central canal and travels upward in the spinothalamic tract to the thalamus. Interneurons bear on the synapse with the second order neurons. C fibers, which are small, slow and localize poorly, can sensitize the larger more potent and rapid Alpha pain fibers in this area. Opiate receptors also operate here (see articles at this site include “Is the term Brain obsolete?”). In central pain, second order fibers, which normally NEVER form a generator current which initiates an action potential, DO gain the ability to do so with nerve injury. Ron Tasker showed that radiostimulation of second order neurons at the neck in patients with Central Pain recreates the central pain. It is believed that the entire length of the nerve axon, or fiber, becomes capable not only of initiating a generator current, but also releases chemicals which cause neighboring uninjured neurons to begin firing automatically, which Marshall Devor named “crossed afterdischarge”.

3rd Order: This neuron travels from the VPM (facial pain) or VPL (body pain) nucleus of the thalamus, both of them on the underside of the thalamus upward to the cortex. PAIN occurs here.

Pain occurs because of a balance between excitation and inhibition, It is influenced by ATTENTION and DISTRACTION.

Located AROUND the neuron and around the synapses are the Microglia, which are involved with growth factors, immune response and regulatory matters concerning the neuron.

The acidifying chemicals, such as cytokines, precursors of the prostaglandins such aarachidonic acid, fatty acids, interleukins, etc operate at ALL SYNAPTIC points. The TRPV1 channel, and the ASIC or acid sensitive ion channel are both located on the far side of the synaptic gap. Neurokinin 1 is at the far side also, as are many other important structures, in what is known as the post synaptic density, so called for its density or image concentrating power under the electron microscope. Many or most of the pain excitatory structures in the PSD are kicked into action by the delivery of calcium, particularly by the N type calcium channel.

Known pain inhibitory structures of the CNS include the periaqueductal gray (see article at this site) and the median raphe nuclei (see using SEARCH).

Brain structures capable of impacting pain include the anterior cingulum, “pretectal nucleus, the reticular formation, the nucleus accumbens, the nucleus tractus solitarii, the amygdala and the reticular thalamic nucleus, this latter being a coincidence detector and a centre for attention and distraction.” (see Knyihar, below)

Bodily location occurs in SI, or the posterior ridge of the central sulcus aka poscentral gyrus while muscle spindle pain goes to the bottom of the sulcus or groove, SII tells the type of pain and is located in the parietal cortex behind SI, while the “painfulness of pain” is located in the insular cortex, which is an infolding just behind the parietal cortex. The prefrontal cortex handles the emotional component attached to pain, in association with other structures in the Papez circuit or Limbic system, including the amygdala.

“Seven levels of nociception and pain are highlighted where pharmacological intervention may be successful,
1. the peripheral nociceptor,
2. the spinal ganglion,
3. the multisynaptic system of the dorsal horn,
4. the modulatory system of the brain stem,
5. the antinociceptive system,
6. the multisynaptic system of the thalamus, and
7. the cortical evaluating and localisation system that is also responsible for descending (inhibiting) control.” See Knyihar below

AS you have already read here, Marshall Devor has identified another pain inhibitory area in the rostral ventral medulla, and Carl Saab has identified the vermis, a midline nucleus in the roof of the cerebellum, as another pain inhibitory area.

Magnetic stimulation of the motor cortex, which is on the forward side of the central sulcus, has been noted to treat central pain. Successful stimulation generally requires open brain surgery. This author has had closed magnetic stimulation without benefit to the central pain. Why motor cortex stimulation should help a sensory problem is not known.

Deep brain implants (electrodes with stimulation) in the thalamus have been tried for central pain without statistically proven results.

See Knyihar and Csillik, Ideggyogy Sz. 2006 Mar 20;59(3-4):87-97.