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Abstract: The nociceptive withdrawal reflex (NWR), a defensive response that allows withdrawal from a noxious stimulus, is a reliable index of spinal nociception in humans. It has been shown that various kinds of stimuli (emotional, visual, auditory) can modulate the transmission and perception of pain. The aim of the present study was to evaluate, by means of the NWR, the modulatory effect on the spinal circuitry of olfactory stimuli with different emotional valence. The magnitude of the NWR elicited by electrical stimulation of the sural nerve was measured while 18 subjects (9 women, 9 men) smelled pleasant, unpleasant, or neutral odors. The NWR was conditioned by odor probe with interstimulus intervals (ISIs) of 500 ms and 1,500 ms. The magnitude of NWR was significantly greater after the unpleasant odor probe (P <.001) and reduced following the pleasant odor probe (P <.001) at both ISIs. A significant effect of olfactory stimuli on subjective pain ratings were found at both ISIs for pleasant vs unpleasant odors (P <.000), and for both pleasant and unpleasant odors vs neutral and basal conditions (P <.000). No statistical differences in subjective pain ratings at different ISIs were found. Consistent with the notion that NWR magnitude and pain perception can be modulated by stimuli with different emotional valence, these results show that olfactory stimuli, too, can modulate spinal nociception in humans. [Copyright &y& Elsevier]

Abstract: In cluster headache (CH), pathogenesis has been emphasized the role of the posterior hypothalamus. It is part of a supraspinal network involved in the descending control of pain, including the diffuse noxious inhibitory control (DNIC), which in turn modulates the pain processing. We hypothesized that CH during the active phase facilitated temporal pain processing supported by abnormal functioning of the DNIC. We studied the functional activity of the DNIC by evaluating the effect of the cold pressor test (CPT) on the temporal summation threshold (TST) of the nociceptive withdrawal reflex. Ten subjects with episodic CH (2 women, 8 men) and 10 healthy subjects were recruited. Each subject underwent neurophysiological evaluation (nociceptive withdrawal reflex TST and related painful sensation) at baseline, then before (control session), during (pain session), and 5min after (aftereffect) the CPT (immersing hand in a 4°C water bath for 4–5min). Patients had been studied during both the active and remission phases. During the active phase, CH revealed a significant facilitation in temporal processing of pain stimuli (reduction of TST), which reverted during the remission phase. The CPT activating the DNIC did not produce any significant inhibitory effect of pain responses in CH during the active phase, whereas it induced a clear inhibition during the remission phase. We hypothesized that in CH, a dysfunction of the supraspinal control of pain related to the clinical activity of the disease, possibly supported by an abnormal hypothalamic function, leads to a facilitation in pain processing and a predisposition to pain attacks. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate the effects of diffuse noxious inhibitory controls (DNICs) on the temporal summation of the nociceptive flexion reflex (RIII reflex) in humans. Recordings were obtained from 36 healthy adults (16 M, 20 F), and the area and temporal summation threshold (TST) of the RIII reflex were measured. The subjective intensity of the painful sensation was rated on an 11-point visual analogue scale (VAS). Neurophysiological and VAS measurements were recorded after activation of DNICs by means of the cold pressor test (CPT), which involved immersing the hand in cold water (2–4°C). A slight significant lower TST was found in the females versus the males. In all the subjects, the CPT induced a significant TST increase and RIII area reduction compared with the control session. The VAS results paralleled those of the RIII reflex area and TST. During the CPT, a significant difference in the percentage TST increase emerged between females and males, being lower in the former. Similarly, we found a significantly lower percentage reduction of the RIII area in women than in men during the CPT. To summarize, activation of DNICs through the CPT significantly increased the TST of the RIII reflex in healthy subjects. This inhibitory effect was gender-specific. Whereas other findings are based on psychophysical evaluations, the results of this experimental study provide an objective neurophysiological demonstration that DNICs attenuate temporal summation in humans and confirm the presence of significant differences in pain modulation mechanisms between men and women. [Copyright &y& Elsevier]