Nociceptive dorsal root ganglion (DRG) neurones have fibres that conduct in the C, Aδ and Aα/β conduction velocity range. The properties of nociceptive compared with non-nociceptive somatic afferent dorsal root ganglion neurones appear to fall into two patterns, A and B. Pattern A properties of nociceptive neurones, the more common type, include longer action potential duration and slower maximum rate of fibre firing, as well as a greater expression of substance P and calcitonin gene-related peptide immunoreactivity. The values of pattern A properties appear to be graded according to the conduction velocity group (C, Aδ or Aα/β) of the fibres. The most pronounced forms of A-type properties are expressed by nociceptive neurones with C-fibres, and these become less pronounced in nociceptive neurones with Aδ-fibres and least pronounced in those with Aα/β fibres (C > Aδ > Aα/β). Some of these properties are also expressed in a less extreme but similarly graded manner through C, Aδ and Aα/β groups of non-nociceptive low threshold mechanoreceptive (LTM) neurone. The less common pattern B properties of nociceptive neurones have similar values in C-, Aδ- and Aα/β-fibre nociceptive neurones but these clearly differ from LTM units with C-, Aδ- and Aα/β-fibre conduction velocities. These features of nociceptive neurones include consistently larger action potential overshoots and longer after-hyperpolarisation durations in nociceptive than in LTM neurones. Experimental Physiology (2002) 87.2, 239-244.

The effects of 7 days of 'dry' water immersion were investigated in six subjects. Changes in the contraction properties were studied in the triceps surae muscle. After immersion, the maximal voluntary contraction (MVC) was reduced by 18.9 % (P < 0.01), and the electrically evoked (150 impulses s-1) maximal tension during tetanic contraction (Po) was reduced by 8.2 % (P > 0.05). The difference between Po and MVC expressed as a percentage of Po and referred to as force deficiency was also calculated. The force deficiency increased by 44.1 % (P < 0.001) after immersion. The decrease in Po was associated with increased maximal rates of tension development (7.2 %) and relaxation. The twitch time-to-peak was not significantly changed, and half-relaxation and total contraction time were decreased by 5.3 % and 2.8 %, respectively, but the twitch tension (Pt) was not significantly changed and the Pt/Po ratio was decreased by 8.7 %. The 60 s intermittent contractions (50 impulses s-1) decreased tetanic force to 57 % (P < 0.05) of initial values, but force reduction was not significantly different in the two fatigue-inducing tests: fatigue index (the mean loss of force of the last five contractions, expressed as a percentage of the mean value of the first five contractions) was 36.2 ± 5.4 % vs. 38.6 ± 2.8 %, respectively (P > 0.05). While identical force reduction was present in the two fatigue-inducing tests, it would appear that concomitant electrical failure was considerably different. Comparison of the electrical and mechanical alterations recorded during voluntary contractions, and in contractions evoked by electrical stimulation of the motor nerve, suggests that immersion not only modifies the peripheral processes associated with contraction, but also changes central and/or neural command of the contraction. At peripheral sites, it is proposed that the intracellular processes of contraction play a role in the contractile impairment recorded during immersion. Experimental Physiology (2002) 87.1, 101-111.

The dorsal horn of the spinal cord plays an important role in transmitting information from nociceptive primary afferent neurones to the brain; however, our knowledge of its neuronal and synaptic organisation is still limited. Nociceptive afferents terminate mainly in laminae I and II and some of these contain substance P. Many projection neurones are located in lamina I and these send axons to various parts of the brain, including the caudal ventrolateral medulla (CVLM), parabrachial area, periaqueductal grey matter and thalamus. The neurokinin 1 (NK1) receptor on which substance P acts is expressed by certain neurones in the dorsal horn, including approximately 80 % of lamina I projection neurones. There is also a population of large NK1 receptor-immunoreactive neurones with cell bodies in laminae III and IV which project to the CVLM and parabrachial area. It has been shown that the lamina III/IV NK1 receptor-immunoreactive projection neurones are densely and selectively innervated by substance P-containing primary afferent neurones, and there is evidence that these afferents also target lamina I projection neurones with the receptor. Both types of neurone are innervated by descending serotoninergic axons from the medullary raphe nuclei. The lamina III/IV neurones also receive numerous synapses from axons of local inhibitory interneurones which contain GABA and neuropeptide Y, and again this input shows some specificity since post-synaptic dorsal column neurones which also have cell bodies in laminae III and IV receive few contacts from neuropeptide Y-containing axons. These observations indicate that there are specific patterns of synaptic connectivity within the spinal dorsal horn. Experimental Physiology (2002) 87.2, 245-249.

This review presents a schematic attempt to classify the major pain pathways, based on the results of recent studies in our laboratory, with a special emphasis on the parabrachial system. Our view is based on results from experiments in the rat, using very small iontophoretic injections of anterograde tracers. As illustrated in this report, we have found a very dramatic difference between ascending projections originating from deep laminae compared with those arising from lamina I of the dorsal horn. We propose three main pain systems and discuss their functional-anatomical relationships. The first system is centred on the projection from deep laminae to three caudal reticular areas - the lateral reticular nucleus (LRN), the subnucleus reticularis dorsalis (SRD) and the gigantocellular lateral paragigantocellular reticular nuclei (NGc) - and the parabrachial internal lateral subnucleus (PBil). The second system is centred on the projection from lamina I to the ventral posterolateral nucleus (VPL), the ventral posteromedial (VPM), the posterior nuclear group (Po) and triangular posterior nucleus (PoT) of the thalamus. The third system is centred on the projection from lamina I to the lateral parabrachial area. We also present the four main projections from the latter area to the extended amygdala, the hypothalamus, the periaqueductal grey matter (PAG), and the ventrolateral medulla (VLM), and their involvement in emotional and autonomic (homeostatic) aspects of pain. Experimental Physiology (2002) 87.2, 251-258.

Painful stimuli can evoke dramatic responses in the cardiovascular and respiratory systems. We have assessed the role of both the sympathetic and parasympathetic nervous system in mediating the reflex tachycardia that accompanies somatic nociception. We describe a major role for the nucleus tractus solitarii (NTS) as a site for integrating nociceptive and cardiorespiratory afferents. Since cardiorespiratory and nociceptive afferents terminate in the NTS, this nucleus offers a powerful opportunity for central modulation. We show that the NTS plays a major role in mediating the reflex tachycardia evoked by somatic noxious stimulation. Similar noxious stimulation attenuates the cardiac component of the peripheral chemoreceptor reflex and inhibits the peripheral chemoreceptor-evoked excitatory synaptic response of some NTS neurones. The functional interpretation we propose is that by depressing homeostatic reflexes at the NTS, noxious stimulation-evoked cardiorespiratory changes can be expressed and maintained, which may be essential for the survival of the animal. Experimental Physiology (2002) 87.2, 259-266.

The endogenous pain control system is composed of multiple functionally distinct brain regions, which are thought to integrate nociceptive information with various brain functions. The clear involvement of some pain control centres in cardiovascular modulation has been claimed as a strong indication of their role in nociceptive-cardiovascular integration. Particular emphasis has been given to their putative function in triggering cardiovascular reactions to pain. However, the possibility of their participation in the less-studied influence of cardiovascular conditions in pain perception has been largely ignored. We have recently addressed this issue by investigating the involvement of the caudal ventrolateral medullary reticular formation (cVLM) in hypertension-induced hypoalgesia. Circuits capable of conveying cVLM-elicited antinociception include a direct reciprocal cVLM-spinal loop, and two disynaptic spinal pathways relaying in rostroventromedial medullary (RVM) neurones and A5 noradrenergic neurones. In the three pathways, the cVLM neurones involved are circumscribed to a small area of reticular formation located laterally to the lateral reticular nucleus, the VLMlat. The VLMlat has a vasodepressor effect similar to that obtained from the cVLM. In the spinal cord dorsal horn, c-fos expression evoked by noxious stimuli is decreased in hypertensive animals, as compared to normotensive animals. In hypertensive animals following lesion of the VLMlat, spinal c-fos expression is identical to that observed in normotensive animals. The collected data point to a role for the VLMlat in the depression of spinal nociceptive processing in response to rises in blood pressure. Since hypertension-induced hypoalgesia is mediated by spinal α2-adrenoreceptors, this effect could be conveyed by the cVLM-A5-spinal pathway. Experimental Physiology (2002) 87.2, 267-274.

It is well established clinically that the affective response to pain of deep origin (muscles, joints and viscera) is distinct from that evoked by cutaneous pain. Cutaneous pain triggers a fight-flight reaction (active emotional coping), whereas deep pain evokes a reaction of quiescence, decreased vigilance and vasodepression (passive emotional coping). These observations led to suggestions of distinct central representations for deep versus cutaneous pain. Indeed, studies using immediate early gene (c-fos) expression revealed selective activation of ventrolateral versus lateral columns of the midbrain periaqueductal grey region (PAG) by persistent pain of deep origin versus intermittent cutaneous pain. Ventrolateral versus lateral PAG activation had been found earlier to evoke passive versus active emotional coping. However, not all cutaneous pain triggers active coping. Persistent cutaneous pain (e.g. burns) instead, usually evokes passive coping. This raised the question of whether the behavioural significance of pain (i.e. its escapability versus inescapability), rather than its tissue origin, is represented in supraspinal regions such as the PAG. Subsequent study revealed that a persistent (inescapable) noxious cutaneous manipulation (clip of the neck) evoked both selective ventrolateral PAG Fos expression and passive emotional coping. Such data suggest that pain representation in the PAG reflects a quality akin to behavioural significance, rather than tissue origin. In contrast, in the spinal cord predominantly superficial dorsal horn Fos expression was seen after either persistent or intermittent noxious cutaneous stimuli, leaving the question of the pathway(s) via which persistent (inescapable) cutaneous pain activates the vlPAG unanswered. One experimental approach to this question is suggested. Experimental Physiology (2002) 87.2, 275-279.

The affective responses to pain arising from deep somatic and visceral tissues differ markedly from those evoked by brief cutaneous insults. Deep pain evokes passive emotional coping that includes quiescence and vasodepression. In contrast, cutaneous pain evokes an active emotional coping: the fight or flight response. There is now considerable evidence to support the notion that nociceptive inputs arising from different peripheral domains drive the different functional columns of the periaqueductal grey (PAG) that co-ordinate either active or passive coping strategies. Nociceptive inputs from deep structures drive neurones in the ventrolateral columns that co-ordinate passive emotional coping whereas brief cutaneous insults activate the dorsolateral/lateral columns that co-ordinate active coping strategies. An emerging concept, as presented in the preceding article by Keay & Bandler, is that it is the behavioural significance of the nociceptive input, rather than its organ of origin per se, that determines the characteristics of the affective response. These authors provide evidence that brief, escapable stimuli activate neurones in the dorsolateral/lateral columns of the PAG and that inescapable, persistent pain, irrespective of its organ of origin, activates the ventrolateral column. This review will present recent evidence that differential representation of escapable and inescapable pain in the PAG extends to distinct representations of 'first' and 'second' pain, as indicated by the columnar distribution of neurones activated by inputs from Aδ- and C-nociceptors. Furthermore, the functional organisation of projections from circumscribed regions of the hypothalamus to the different columns of the PAG indicates that the behavioural significance of the pain signal is represented in brain regions other than the PAG. Experimental Physiology (2002) 87.2, 281-286.