Stuart Clark

Pain processing during three levels of noxious stimulation produces differential patterns of central activity

&NA; Previous functional imaging studies have demonstrated a number of discrete brain structures that increase activity with noxious stimulation. Of the commonly identified central structures, only the anterior cingulate cortex shows a consistent response during the experience of pain. The insula and thalamus demonstrate reasonable consistency while all other regions, including the lentiform nucleus, somatosensory cortex and prefrontal cortex, are active in no more than half the current studies. The reason for such discrepancy is likely to be due in part to methodological variability and in part to individual variability. One aspect of the methodology which is likely to contribute is the stimulus intensity. Studies vary considerably regarding the intensity of the noxious and non‐noxious stimuli delivered. This is likely to produce varying activation of central structures coding for the intensity, affective and cognitive components of pain. Using twelve healthy volunteers and positron emission tomography (PET), the regional cerebral blood flow (rCBF) responses to four intensities of stimulation were recorded. The stimulation was delivered by a CO2 laser and was described subjectively as either warm (not painful), pain threshold (just painful), mildly painful or moderately painful. The following group subtractions were made to examine the changing cerebral responses as the stimulus intensity increased: (1) just painful − warm; (2) mild pain − warm; and (3) moderate pain − warm. In addition, rCBF changes were correlated with the subjective stimulus ratings. The results for comparison ‘1’ indicated activity in the contralateral prefrontal (area 10/46/44), bilateral inferior parietal (area 40) and ipsilateral premotor cortices (area 6), possibly reflecting initial orientation and plans for movement. The latter comparisons and correlation analysis indicated a wide range of active regions including bilateral prefrontal, inferior parietal and premotor cortices and thalamic responses, contralateral hippocampus, insula and primary somatosensory cortex and ipsilateral perigenual cingulate cortex (area 24) and medial frontal cortex (area 32). Decreased rCBF was observed in the amygdala region. These responses were interpreted with respect to their contribution to the multidimensional aspects of pain including fear avoidance, affect, sensation and motivation or motor initiation. It is suggested that future studies examine the precise roles of each particular region during the central processing of pain.

Quantifying digital vascular disease in patients with primary Raynaud’s phenomenon and systemic sclerosis

In primary and secondary Raynaud’s phenomenon, measurement of activity or severity, or both, of the digital vascular disease is a major challenge. We need to identify objective measures of digital vascular disease that are helpful in predicting those patients with Raynaud’s who have underlying connective tissue disease, and to measure reliably digital vascular disease progression, and responses to treatment. None of the various physiological measurement techniques used in the assessment of patients with primary or secondary Raynaud’s are ideal. In this review we outline these techniques, highlighting their applications and limitations. The discussion concentrates on the physiological assessment of patients with primary Raynaud’s phenomenon (PRP) and systemic sclerosis (SSc), but is also applicable to other connective tissue diseases. We have not included biochemical markers of vascular injury or measurement of tissue oxygen levels. In PRP, episodic ischaemia in response to cold exposure or to emotional stimuli is entirely reversible: absence of tissue damage is a defining feature.1 In contrast, SSc may be associated with irreversible tissue damage with ulceration, scarring and sometimes gangrene, and structural change occurs in the vasculature.2 3 Indeed, SSc is probably primarily a disease of the vasculature, although it is not clear how this interrelates with collagen and other connective tissue matrix metabolism.4 5 Assessment of digital vascular disease needs to take into account: (a) Digital vasospasm. This is best assessed by dynamic testing with standard stimuli, such as a standard cold stress. (b) Structural vascular disease. This may affect basal blood flow in addition to vascular responses to standard stimuli. In the patient presenting with Raynaud’s phenomenon, we must assess both the microvasculature and the digital arteries. Different physiological measurement techniques may be used in combination, especially if investigators wish to examine both digital artery and microvascular flow.6 On widefield capillaroscopy, …

Laser stimulation for pain research

Pain is a serious medical problem; it inflicts huge economic loss and personal suffering. Pain signals are conducted via small, non- and partially myelinated A-delta and C nerve fibers and lasers are particularly well suited to stimulating these fibers. Large myelinated fibers convey touch and vibration information and these fibers are also discharged when contact thermodes and other touch pain stimuli are used and this would give a more muddled signal for functional imaging experiments. The advantages of lasers over conventional methods of pain stimulation are good temporal resolution, no variable parameters are involved such as contact area and they give very reproducible results. Accurate inter-stimulus changes can be achieved by computer control of the laser pulse duration, pulse height and repetition rate and this flexibility enables complex stimulation paradigms to be realized. We present a flexible carbon dioxide laser system designed to generate these stimuli for the study of human cerebral pain responses. We discuss the advantages within research of this system over other methods of pain stimulation such as thermal, electrical and magnetic. The stimulator is used in conjunction with functional magnetic resonance imaging, positron emission tomography and electrophysiological methods of imaging the brains activity. This combination is a powerful tool for the study of pain-induced activity in different areas of the brain. An accurate understanding of the brains response to pain will help in research into the areas of rheumatoid arthritis and chronic back pain.