Cerebral responses to a continual tonic pain stimulus measured using positron emission tomography S.W.G. Derbyshire a, *, A.K.P. Jones b a PET Facility, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA b University of Manchester Rheumatology Department, Hope Hospital, Salford M6 8HD, UK Received 19 June 1997; received in revised form 7 December 1997; accepted 3 February 1998 Abstract We have previously demonstrated the localised positron emission tomographic cerebral correlates of the experience of painful phasic heat in the normal human brain. In this study we examine whether these responses are different using a continuous, tonic heat stimulus. The regional cerebral responses to non-painful and painful thermal stimuli in 12 male subjects were studied by monitoring serial measurements of regional cerebral blood flow (rCBF) with positron emission tomography (PET) using H 2 15 O. Significantly increased rCBF responses to tonic noxious stimulation compared with non-noxious stimulation were observed bilaterally in the anterior cingulate (Brodmann’s area (BA) 24) cortex. Contralateral responses were observed in the lentiform nucleus and posterior insula cortex and ipsilateral responses were observed in the thalamus, cerebellum, prefrontal (BA 10) cortex and anterior insula cortex. These findings demonstrate general agreement between the main areas of cerebral activation during both phasic and tonic pain.  1998 International Association for the Study of Pain. Published by Elsevier Science B.V. Keywords: Cerebral response; Tonic heat stimulus; Regional cerebral blood flow; Phasic pain; Tonic pain; Positron emission tomography 1. Introduction Pain is an experience that comprises sensory-discrimina- tive and motivational-affective components (Melzack and Casey, 1968). Positron emission tomography (PET) is able to measure cerebral responses to different components of experimental pain using changes in regional cerebral blood flow (rCBF) as a marker of neuronal activity. Previous experiments have used a standardised experimental phasic pain stimulus and have weighted the experimental design to measure the motivational-affective and temperature discri- mination components. Subtracting the effects of non-nox- ious heat from noxious-heat stimuli eliminates the tactile sensory-discriminative components relating to texture and position of the acute noxious stimulus but not the compo- nents relating to stimulus intensity (Jones et al., 1991; Tal- bot et al., 1991; Casey et al., 1994; Coghill et al., 1994; Derbyshire et al., 1994; Vogt et al., 1996). The central structures that have been shown to demonstrate significant increases in rCBF in response to phasic pain include the brain stem, thalamus, lentiform nucleus (putamen and stria- tum), and inferior parieto-temporal, prefrontal (Brodmann’s area (BA) 9/10 and 44/46), insular and anterior cingulate (BA 24) cortices. The anterior cingulate and insular cortices contain some of the main cortical projections of the medial pain system projecting via the medial thalamic nuclei. The latter receive a polysynaptic input from the brain stem, in addition to collateral input from the spinothalamic tract. Direct and indirect inputs to anterior cingulate cortex from the medial thalamic nuclei and lentiform nuclei are well documented in addition to reciprocal connections with inferior parieto-temporal cortices (Hoesen et al., 1993). The affective and sensory components of pain are thought to be present to varying degrees depending on the type of pain stimulus. Specifically, phasic pain stimuli are consid- ered less unpleasant or bothersome than tonic stimuli and are relatively resistant to morphine analgesia (Chen and Treede, 1985; Cooper et al., 1986; Rainville et al., 1992). Sternbach (1976) suggested that tonic pain may be psycho- logically more similar to chronic pain, although this is based Pain 76 (1998) 127–135 0304-3959/98/$19.00  1998 International Association for the Study of Pain. Published by Elsevier Science B.V. PII S0304-3959(98)00034-7 * Corresponding author. Tel.: +1 412 6470736; fax: +1 412 6470700.