We have always said neuropathic pain was different, but even we were not quite prepared for this article, provided it can be reproduced.
First, a review of brain anatomy. Running side to side about midway back is a groove, the central sulcus. In back is SI or the sensory cortex, in front is MI or the primary motor cortex. On the side of the brain is the parietal area, at the base of which is SII, or secondary sensory area, and behind this is the insular cortex. Recent MRI has shown that pain location is in SI, pain type is coded in SII, and the painfulness of pain is generated by the insula. Paying attention to all this is the cingulate gyrus or ridge which is more toward the front and deep in the brain.
However, despite the traditional assignments of pain to SENSORY and muscle activity to MOTOR cortex, Peyron et al shook things up a little bit by studying allodynia (pain from nonpainful stimulus) in those with central pain (or other nerve injury pain) on one side of the body. We understand why Peyron would want to compare someone who was pained on one side and normal on the other, it makes comparison easy on fMRI, but we wish he would follow up with pure bilateral CP.
You will recall that pain crosses over in front of the central canal of the cord and ascends in the spinothalamic tract, winding up in the CONTRALATERAL or opposite side thalamus. There is however, the knowledge that the very bizarre marginal cells in Rexed Layer I, the very outermost layer of the dorsal horn of the cord, can sensitize huge areas, sometimes even single fibers can sensitize the entire half of the body. The unique thing about pain going up in the marginal layer is that it stays on the same side of the cord, or in other words is IPSILATERAL.
Now you can consider Peyron et al for yourself. See at NEUROLOGY 2004;63:1838-1846
“An fMRI study of cortical representation of mechanical allodynia in patients with neuropathic pain”.
Unfortunately, Peyron did not separate his subjects into central pain vs. peripheral nerve injury, but the fact he seems to have found no differences is in itself significant. Perhaps there are none.
These French researchers found that “When applied to the normal side, brush and cold rubbing stimuli did not evoke pain and activated a somatosensory “control” network including contralateral primary (SI) and secondary (SII) somatosensory cortices and insular regions.”
Things changed of course, when the subjects were allodynic from central injury. “The same stimuli became severely painful when applied to the allodynic side and activated regions in the contralateral hemisphere that mirrored the “control” network, with, however, lesser activation of the SII and insular cortices. Increased activation volumes were found in contralateral SI and primary motor cortex (MI).”
Already we are noticing that the motor cortex is acting up on the contralateral side, ie away from the injury. WHY???We don’t know. The MOTOR cortex is supposed to be MOTOR, but apparently, it just isn’t.
Then they pick up what seems suspicious for marginal layer activity.
“Whereas ipsilateral responses appeared very small and restricted after control stimuli, they represented the most salient effect of allodynia and were observed mainly in the ipsilateral parietal operculum (SII), SI, and insula. Allodynic stimuli also recruited additional responses in motor/premotor areas (MI, supplementary motor area), in regions involved in spatial attention (posterior parietal cortices), and in regions linking attention and motor control (mid-anterior cingulate cortex).”
You notice here the not unexpected involvement of the cingulate cortex which is front and middle in the brain, and has long been known to be associated with attentional aspects of pain. What is really surprising is the ipsilateral motor areas responding. Pain is supposed to cross over. We must be outside the conventional pain pathways. Perhaps we are seeing this through the marginal layer sensitization, but one also has to wonder about the autonomic nervous system, the unconscious nervous system, which can reach brain via a journey with blood vessels, and bypasses the cord.
Thanks to Peyron, whose study remains as one of the few focused on central pain, even though he dealt primarly with those who had CP only on one side. We still don’t know how this would turn out with the typical SCI patient who is damaged on both sides.
Peyron uses good language when he concludes there is a “shift of perception from innocuous toward painful and ill-defined sensations”. If he can get away with this, so can we.