Body-site effect on CPM efficiency in healthy subjects: Central vs. peripheral stimulation.

Structural changes in the peripheral nerve system in neuropathic states alter sensory capacity of the affected area, thus biasing results of conditioned pain modulation (CPM) responses. The aim of this study was to evaluate CPM efficiency of central (i.e. trunk) vs. peripheral (i.e. limb) application of 'test' and 'conditioning' stimuli. Methods: Healthy volunteers (ages 18-73 yrs) underwent two CPM protocols: 'CPM Limb' and 'CPM Trunk'. Each included two types of test stimuli (Ts) (pressure pain threshold: PPT; and contact heat) conditioned either to hand immersion in cold noxious water (CPM limb), or to noxious contact heat applied on lower back (CPM trunk). Results: Both protocols generated efficient pain inhibition for each of the applied Ts; the PPT-based protocol induced more efficient CPM when the conditioned stimulus was applied on the trunk (p = 0.016). Moreover, the PPT-based CPM responses were significantly correlated (ρ = 0.349; p = 0.007). Conclusions: An efficient CPM induced by both central and peripheral stimulation, along with significant correlation between PPT-based responses, advances using the central 'CPM Trunk' protocol in patients with peripheral neuropathy.

Electrophysiological and psychophysical correlates of spatial summation to noxious heat: the possible role of A-delta fibers.

Although spatial summation of pain (SSP) is central to the processing of pain intensity and quality, its mechanism is not fully understood. We previously found greater heat SSP in hairy than in glabrous skin, suggesting that perhaps A-mechano-heat II (AMH-II) nociceptors are the dominant subserving system. In order to further explore the role of A-delta fibers in heat-induced SSP, we analyzed the electrophysiological correlates of SSP under conditions that minimize the influence of skin thicknesses. Among 17 subjects, fast rate of rise (70 °C/sec) heat stimuli that induced a pre-fixed, similar, SSP magnitude for hairy and glabrous skin were repeatedly administered using large and small probes, during which time the contact heat-evoked potentials (CHEPs) and pain ratings were recorded. Both N2 and P2 amplitudes were larger in hairy than in glabrous skin, but a differential effect of SSP was found on the CHEPs. Despite similar psychophysical SSP in hairy and glabrous skin, the electrophysiological SSP reflected in N2 but not P2 amplitude was larger in hairy skin. Nevertheless, regardless of skin type, SSP was manifested by an increase in P2 amplitudes. Considering the uniform psychophysical SSP for the two skin types, the fast stimulation rate and lower activity of AMH-II in glabrous skin, a greater electrophysiological SSP in hairy than in glabrous skin may suggest that SSP is mainly subserved by AMH nociceptors. The overall SSP effect, manifested in greater P2 amplitude, may reflect specific brain responses aimed to prepare the individual to an increased potential tissue damage.

'Virtual lesion' in pain research; a study on magnetic stimulation of the primary motor cortex.

BACKGROUND: 'Virtual lesion' ('VL') is a transient disruption of cortical activity during task performance. It can be induced by single pulses or short trains of transcranial magnetic stimulation (TMS) directed to functionally relevant brain areas. We applied 'VL' methodology of a short train of TMS given on top of experimental tonic pain, expecting to see changes in pain scores. METHODS: Thirty young healthy subjects (15 women) were assessed with active ('VL') or 'sham' TMS in different sessions, randomly. In each session, 30 sec-long contact heat (47.5 °C, right forearm) was applied stand-alone ('baseline') and with 5 sec-long 10 Hz-TMS over left primary motor cortex (M1) starting at 17 sec of the heat stimulation. RESULTS: Pain scores decreased after 'VL' or 'sham' (p < 0.001). Independently of the type of TMS, pain reduction was stronger in women (p = 0.012). A triple Sex x Stimulation type ('VL' or 'sham') x Condition ('baseline' heat pain vs. heat pain with TMS) interaction (p = 0.027) indicated stronger pain reduction by 'VL' in women (p = 0.008) and not in men (p = 0.78) as compared to 'baseline'. Pain catastrophizing and perceived stress ratings affected the model (p = 0.010 and p < 0.001, respectively), but without sex differences. CONCLUSIONS: This study indicates that interactions between cortical excitability of the motor cortex and nociceptive processing may be gender-related.

Associations between autonomic dysfunction and pain in chemotherapy-induced polyneuropathy.

BACKGROUND: Autonomic neuropathy, a relatively common complication of several chemotherapy agents, can affect the vagus nerve and its pain inhibitory capacity, thus increasing sensitivity to pain. This study aimed to evaluate the relationships between autonomic parasympathetic function and the perception of (1) spontaneous pain; (2) experimental non-painful sensations; and (3) experimental painful sensations in chemotherapy-induced neuropathy patients. METHODS: Twenty-seven cancer patients with chemotherapy-induced polyneuropathy were enrolled (20 women, age 56.6 ± 7.9). Autonomic parameters of heart rate variability, deep-breathing and Valsalva ratios, experimental non-painful parameters of warm, cold and mechanical detection thresholds, and painful parameters of heat pain thresholds, pain rating of suprathreshold stimulus, mechanical temporal summation and conditioned pain modulation response were examined. RESULTS: Autonomic parameters and spontaneous pain levels were not associated, yet autonomic parameters were positively correlated with non-painful sensations - milder autonomic neuropathy was accompanied by milder sensory neuropathy as indicated by several parameters, e.g., lower Valsalva ratio was correlated with higher warmth detection threshold (r = -0.465; p = 0.033). Autonomic parameters were, however, negatively correlated with painful sensations - lower parasympathetic-vagal activity was associated with higher pain sensitivity as indicated by several parameters, e.g., lower Valsalva ratio was correlated with higher pain rating of suprathreshold stimulus (r = -0.559; p = 0.008). CONCLUSIONS: Diminished vagal function due to neuropathy is associated with, and may possibly underlie, pain disinhibition expressed as greater levels of experimental pain.

Asymmetric pain processing in Parkinson's disease.

BACKGROUND AND PURPOSE: Reduced endogenous pain inhibition, as part of the degenerative process, is presumed to be the mechanism underlying the common presence of pain in patients with Parkinson's disease (PD). The present study aimed to assess an endogenous pain inhibitory system in PD using the conditioned pain modulation paradigm. METHODS: Twenty-six predominantly unilateral PD patients and 19 controls underwent psychophysical pain assessment before and after patients' morning dopaminergic medication. RESULTS: An unexpected increase in several parameters of pain perception for PD patients was found after dopaminergic medication (e.g. for 49°C noxious heat stimulation an increase from 70.6 ± 4.0 to 77.6 ± 4.0 on the numerical pain scale, P < 0.001). This increase was seen in patients with predominantly left-sided PD, regardless of the stimulated side (for 49°C noxious heat stimulation, predominantly left-sided PD patients, pain perception increased from 73.5 ± 6.8 to 85.0 ± 6.8, P < 0.001, whereas predominantly right-sided PD patients did not show a significant increase, 68.3 ± 6.8 to 70.4 ± 6.5, P = 0.777). Baseline efficiency of conditioned pain modulation inversely correlated with age at disease onset (r = -0.522; P = 0.009) and disease severity (Unified PD Rating Scale, r = 0.447; P = 0.032) but did not differ between patients and controls. CONCLUSIONS: Increased sensory response causing hyperalgesia occurs after dopaminergic medication in patients with predominantly left-sided PD.

Simultaneous recording of late and ultra-late pain evoked potentials in fibromyalgia.

OBJECTIVE: To characterize laser evoked potentials (LEP), pain psychophysics and local tissue response in fibromyalgia patients. METHODS: LEP were recorded in 14 women with fibromyalgia in response to bilateral stimulation of tender and control points in upper limbs by 4 blocks of 20 stimuli at each point. Subsequently, heat pain thresholds were measured and supra-threshold magnitude estimations of heat pain stimuli were obtained on a visual analogue scale. Finally, the extent of the local tissue response induced by the previous stimuli was evaluated. RESULTS: Laser stimuli elicited two long latency waves: A late wave (mean latency 368.9+/-66.9 ms) in most patients (13/14) from stimuli at all points, and an ultra-late wave (mean latency 917.3+/-91.8 ms) in 78.5% of the patients at the control points and in 71.4% at the tender points. Amplitude of ultra-late waves was higher at the tender points (20.67+/-11.1 microV) than at the control points (10.47+/-4.1 microV) (P=0.016). Pain thresholds were lower in the tender (41.2+/-2.7 degrees C) than the control points (43.9+/-3.2 degrees C) (P=0.008). Local tissue response was significantly more intense at tender than control points (P=0.004). CONCLUSIONS: Ultra-late laser evoked potentials can be recorded simultaneously with late potentials. Our findings are compatible with presence of peripheral C-fiber sensitization, mostly at tender points, probably combined with generalized central sensitization of pain pathways in fibromyalgia.

Pain perception in women with dysmenorrhea.

OBJECTIVE: To determine if systemic processing of pain differs in women with and without dysmenorrhea. METHODS: Twenty-two dysmenorrheic women and 31 nondysmenorrheic women were studied by pain threshold and supra-threshold magnitude estimation to heat stimuli, pain-evoked potentials by laser stimuli, and anxiety scores four times across their menstrual cycles. RESULTS: Significant differences were found between dysmenorrheic and nondysmenorrheic women. In all four examinations across the menstrual cycle, dysmenorrheic women had longer latencies of pain-evoked potentials (383.08 +/- 6.8 msec versus 345.05 +/- 7.0 msec, P <.001), higher magnitude estimations on visual analog scale of supra-threshold pain (83.29 +/- 2.87 versus 63.50 +/- 3.82, P <.001), and higher state anxiety scores (37.69 +/- 1.7 versus 29.20 +/- 1.9, P =.002). CONCLUSION: Women with dysmenorrhea show enhanced pain perception compared to nondysmenorrheic women. This augmentation of pain perception may be part of the development of dysmenorrhea.

P300 and stress in mild head injury patients.

OBJECTIVE: The P300 component of event-related potentials is affected by personal meaningfulness of the stimulus to the subject. Thus, the P300 component could provide an objective parameter in the emotional assessment of road accident mild head injury patients, when exposed to relevant stimuli. METHODS: Thirteen patients with post-traumatic symptoms and 14 healthy controls were evaluated in this study. Two word types, distinguished by color, were presented on a computer screen in active 'oddball' paradigm conditions. In the first subtest, the targets were accident-related (stressful) words; in the second subtest, the targets were non-accident-related (neutral) words. Target (20%) and non-target (80%) were defined by word color. Data recorded from Pz were analyzed for P300 parameters. RESULTS: Patients and controls differed in their reaction to word types (group x word main effect P = 0.0089), regardless of the oddball presentation. Overall, accident-related words produced a significantly larger P300 wave than neutral words in patients (P = 0.0001), but not in controls (P = 0.5741). Significant correlation was found between combined P300 amplitude difference (all stressful words vs. all neutral words) and the patient's Zung state anxiety score (r = 0.68, P = 0.01). CONCLUSION: We suggest the P300 component can provide a useful, objective tool in the assessment of mild head injury patients.