Distributed processing of pain and vibration by the human brain

Abstract

Pain is a diverse sensory and emotional experience that likely involves activation of numerous regions of the brain. Yet, many of these areas are also implicated in the processing of nonpainful somatosensory information. In order to better characterize the processing of pain within the human brain, activation produced by noxious stimuli was compared with that produced by robust innocuous stimuli. Painful heat (47-48 degrees C), nonpainful vibratory (110 Hz), and neutral control (34 degrees C) stimuli were applied to the left forearm of right-handed male subjects. Activation of regions within the diencephalon and telencephalon was evaluated by measuring regional cerebral blood flow using positron emission tomography (15O-water-bolus method). Painful stimulation produced contralateral activation in primary and secondary somatosensory cortices (SI and SII), anterior cingulate cortex, anterior insula, the supplemental motor area of the frontal cortex, and thalamus. Vibrotactile stimulation produced activation in contralateral SI, and bilaterally in SII and posterior insular cortices. A direct comparison of pain and vibrotactile stimulation revealed that both stimuli produced activation in similar regions of SI and SII, regions long thought to be involved in basic somatosensory processing. In contrast, painful stimuli were significantly more effective in activating the anterior insula, a region heavily linked with both somatosensory and limbic systems. Such connections may provide one route through which nociceptive input may be integrated with memory in order to allow a full appreciation of the meaning and dangers of painful stimuli. These data reveal that pain-related activation, although predominantly contralateral in distribution, is more widely dispersed across both cortical and thalamic regions than that produced during innocuous vibrotactile stimulation. This distributed cerebral activation reflects the complex nature of pain, involving discriminative, affective, autonomic, and motoric components. Furthermore, the high degree of interconnectivity among activated regions may account for the difficulty of eliminating pathological pain with discrete CNS lesions.

A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy

“…Acute phasic noxious stimulation has been used in most of these studies. Apart from some inconsistencies, there is a general consensus that such stimuli activate the anterior cingulate cortex (ACC) and the mid-/anterior insula of the medial pain system as well as the primary-and secondary somatosensory cortices (S1 and S2) of the lateral pain system Talbot et al, 1991;Casey et al, 1994Casey et al, , 1996Coghill et al, 1994;Apkarian, 1995;Davis et al, 1995Davis et al, , 1997Hsieh, 1995;Vogt et al, 1996). These ®ndings support the hypothesis that the experience of pain is processed in a parallel interactive and distributed fashion.…”

“…First, the contrasts Allodynia -Rest, Allodynia -Contralateral touch, Rest -Allodynia, Contralateral touch -Allodynia and Contralateral touch -Rest were analyzed, using a multisubject with replications design (3 conditions, 5 blocks (subjects)). The rCBF increases were investigated in a pre-de®ned pain network based on previous functional imaging studies of pain (Di Piero et al, 1991, 1994Jones et al, 1991;Talbot et al, 1991;Apkarian et al, 1992Apkarian et al, , 1995Casey et al, 1994Casey et al, , 1996Coghill et al, 1994;Davis et al, 1995;Drevets et al, 1995;Hsieh, 1995;Hsieh et al, 1995a,b;Iadarola et al, 1995;Craig et al, 1996;Vogt et al, 1996). The pain network included the contralateral S1 and, bilaterally, the thalamus, S2, insula, ACC and the periaqueductal gray (PAG).…”

“…The pain network included the contralateral S1 and, bilaterally, the thalamus, S2, insula, ACC and the periaqueductal gray (PAG). Similarly, the contralateral S1 and S2 were chosen for the innocuous somatosensory control condition based on previous functional imaging studies of non-painful vibratory sensibility (Fox et al, 1987;Burton et al, 1993;Coghill et al, 1994). The location of the secondary somatosensory cortex (S2) has been de®ned anatomically in the dorsal bank of the lateral sulcus in the parietal operculum of the monkey (Roberts and Akert, 1963).…”

Bilateral behavioral and regional cerebral blood flow changes during painful peripheral mononeuropathy in the rat

“…The involvement of limbic structures in nociceptive processing and of structures associated with pain modulation is expected because the limbic system has long been believed to play an important role in neural mechanisms related to the affective-motivational dimension of pain (Melzack and Casey, 1967;Hylden et al, 1986;Geisler et al, 1994;Chapman, 1996;Willis and Westlund, 1997). Recent studies using positron emission tomography also report significant increases in regional blood flow in limbic forebrain structures during acute or chronic pain perception in humans (Talbot et al, 1991;Jones et al, 1991;Casey et al, 1994Casey et al, ,1996Coghill et al, 1994;Hsieh et al, 1995Hsieh et al, ,1996Vogt et al, 1996). Anatomical studies have shown that limbic structures receive spino-reticulo-thalamic input via connections from the thalamic medialintralaminar nuclei and thalamic reticular nucleus Robertson and Kaitz, 1981).…”

“…Substantial evidence shows that increases in regional cerebral blood flow (rCBF) are tightly and positively coupled to increases in synaptic glucose metabolism and electrical activity (Sokoloff, 1978;Sokoloff, 1981;Mraovitch et al, 1992;Malonek and Grinvald, 1996). Studies in humans using positron emission tomography (PET) have revealed unique patterns of changes in rCBF that are associated with the perception of pain Talbot et al, 1991;Casey et al, 1994;Coghill et al, 1994). Such studies provide insights into the function of the pain network as a whole; information that was previously unattainable from clinical data or individual pharmacological, stimulation, lesion or electrophysiological experiments.…”