Diffuse noxious inhibitory controls triggered by heterotopic CO2 laser conditioning stimulation decreased the SEP amplitudes induced by electrical tooth stimulation with different intensity at an equally inhibitory rate

The purpose of this study was to investigate (1) whether selective Adelta-fiber stimulation with CO(2) laser produces a diffuse noxious inhibitory controls (DNIC) effect in the trigeminal nerve territory; and (2) whether the DNIC effect differs depending on test stimulus intensities under constant conditioning stimuli. To examine whether the CO(2) laser radiation on the dorsum of the hand selectively stimulates Adelta-fibers, laser evoked potentials (LEP) were recorded. The mean peak latency of LEP was 381.4 ms. The findings revealed that the CO(2) laser selectively stimulated Adelta-fibers. Electrical tooth stimuli with 3 levels of intensities (1.2, 1.4, 1.6 times the pain threshold) were applied to subjects as test stimulation in randomized order, with a CO(2) laser stimulus of 18 mJ/mm(2) applied to the dorsum of the hand for 4 min as the noxious conditioning stimulus. Somatosensory evoked potentials (SEP) induced by electrical tooth stimulation were recorded and tooth pain intensity was evaluated using a visual analogue scale (VAS). The amplitudes of the SEP late component and VAS values were significantly decreased only during the conditioning stimuli without aftereffect. The inhibitory rates of the amplitudes ranged from 31.3% to 34.6% and the VAS values from 29.0% to 31.2%. There were no significant differences in their inhibitory rates between the 3 test stimulus intensities. The result indicated that selective Adelta-fiber stimulation with the CO(2) laser produces a DNIC effect in the trigeminal nerve territory and suggested that the DNIC effect does not depend on the intensity of the test stimuli.     

Gender differences in pain modulation by diffuse noxious inhibitory controls: A systematic review

Over the last decade, extensive research has demonstrated sex differences in pain perception and modulation. Several factors have been proposed to account for the differences observed between men and women, including pain modulation through diffuse noxious inhibitory controls (DNIC). Studies investigating sex differences in DNIC have shown mixed results, with some reporting decreased DNIC effect in women compared with men, while others found no difference in DNIC between the sexes. Additional studies have investigated DNIC in both sexes without focusing on sex differences. This systematic review aimed to answer the following question: “In humans of reproductive age without chronic pain, are women more likely than men to have decreased Diffuse Noxious Inhibitory Controls?” Relevant studies were identified by computerized searches of Pubmed/Medline, Embase, Biosis, Web of Science, PsycInfo and Cochrane (from January 1980 through February 2009). The search was limited to human studies with no language restriction.     

Diffuse noxious inhibitory control evoked by tonic craniofacial pain in humans

Tonic pain in one body segment can inhibit the perception of pain in another body segment. This phenomenon is mediated by diffuse noxious inhibitory controls (DNIC), and its efficacy in craniofacial regions is investigated in this study. A compressive device that evoked a tonic, moderate/severe, headache‐like, conditioning pain (～8/10 on a visual analogue scale) was applied for 15 min. Eleven males participated in the study. Pressure pain threshold (PPT) and pressure pain tolerance (PPTol) at multiple heterosegmental body sites (right masseter, splenius capitis, second intermediate phalange, brachioradialis and tibialis anterior) were measured before, during and at multiple time points (5, 20 and 35 min) after the termination of the conditioning pain. PPTs and PPTols were compared within participants across two experimental sessions; one that included painful conditioning stimulation, and a separate control session on a different day. Painful conditioning increased PPT significantly during pain over the masseter (p <0.05) and over the tibialis anterior (p <0.01). PPTol was unchanged. In the period after the painful conditioning stimulation PPT was depressed compared to control. This study shows that pain evoked from the craniofacial region evokes DNIC‐like mechanisms on segmental as well as heterosegmental sites.     

经皮电神经刺激不同部位对脑卒中患者体感诱发电位的影响

目的比较单次（45min）经皮电神经刺激（TENS）不同部位治疗脑卒中患者患侧肢体对体感诱发电位（SEP）的影响。方法按TENS的治疗部位将14例脑卒中患者分为2组：同时刺激偏瘫侧上、下肢组（上下肢组）8例和单独刺激偏瘫侧上肢组（上肢组）6例。2组患者分别接受1次45min的TENS治疗，刺激频率为100Hz，脉宽为200μs，强度为患者最大耐受量。分析双侧上、下肢或双上肢SEP检测过程中N9和N20的波幅及潜伏期，比较同一测试时间点SEP的重复检测信度，并比较两种不同治疗方法所得到的SEP结果差异。结果2组患者2次检测的SEP值等级间相关系数（ICC）值为0．9006—1．0000，上肢组优于上下肢组。治疗前、后比较，上下肢组的N9和N20波幅及潜伏期无明显变化，而上肢组N9及N20波幅增高，潜伏期缩短，以N20的改变更为显著。治疗前2组患者SEP值比较，差异有统计学意义（P〈0．05），故以治疗前SEP值为协变量进行统计学分析，治疗后2组患者SEP值差异有统计学意义（P〈0．01）。结论单次45min的TENS治疗能改善脑卒中患者偏瘫肢体的SEP值，单独刺激上肢或同时刺激上下肢均有较高的可重复性，但单独刺激上肢的方法可重复性更高，SEP值的改变更明显。     

经皮电神经刺激穴位治疗对脑卒中患者偏瘫侧上肢体感诱发电位的影响

目的：比较单次（45min）经皮电神经刺激（TENS）穴位治疗对脑卒中患者偏瘫侧上肢体感诱发电位（SEP）的影响。方法：符合入选条件并签署知情同意书的29例初发脑卒中患者分层后随机分为治疗组和安慰组。治疗组患者接受1次45minTENS治疗,刺激电极放在患侧上肢穴位上,刺激频率为100Hz,脉宽为200μs,强度为患者最大耐受量;安慰组患者接受45min安慰治疗,仪器与治疗组相同,有指示灯闪,但无电流输出。两组患者分别在治疗前后接受1次SEP检测,并比较其治疗前后的差异。结果：治疗前两组患者偏瘫侧与健侧SEP值相比,除N9潜伏期外差异均有显著性意义（P〈0.05）;治疗组治疗前后SEP值差异有显著性意义（P〈0.05）;治疗后两组患者组间SEP值N20潜伏期差异有显著性意义（P〈0.05）。结论：单次45minTENS治疗能改善脑卒中患者偏瘫侧上肢的SEP,推测TENS改善脑卒中偏瘫患者肢体功能可能与TENS增加脑电活动,改善SEP,激活脑细胞的功能活动有关。     

The effect of trigeminal nociceptive stimulation on blink reflexes and pain evoked by stimulation of the supraorbital nerve

The aim of this study was to investigate the effect of painful conditioning stimuli on pain and blink reflexes to supraorbital nerve stimulation. Electromyograph activity was recorded bilaterally from the orbicularis oculi muscles in 13 normal participants in response to low (2.3 mA) and high-intensity (18.6 mA) electrical stimulation of the left supraorbital nerve before, during and after the application of ice to the left or right temple or immersion of the left hand in ice-water for 60 s. The pain evoked by the high-intensity electrical stimulus was greater during painful conditioning stimulation of the ipsilateral temple than during the recovery period afterwards, and was greater than during painful conditioning stimulation of the contralateral temple. These findings imply that spatial summation of nociceptive signals across different divisions of the trigeminal nerve can heighten pain. However, painful conditioning stimulation, particularly to the right temple, strongly suppressed the R2 component of the blink reflex to the low-intensity stimulus, and also suppressed R2 to the high-intensity stimulus. Thus, an inhibitory influence (e.g. diffuse noxious inhibitory controls) appeared to mask ipsilateral segmental facilitation of R2 during ice-induced headache. This finding contrasts with recent electrophysiological evidence of trigeminal sensitization in migraine.     

Inhibitory effects do not depend on the subjective experience of pain during heterotopic noxious conditioning stimulation (HNCS): a contribution to the psychophysics of pain inhibition.

Heterotopic noxious conditioning stimulation (HNCS) has been thought to give access to the diffuse noxious inhibitory controls (DNIC) in man, which can be activated in wide-dynamic-range neurons by noxious stimulation from remote areas of the body and form the neurophysiological basis of the phenomenon 'pain inhibits pain'. The latter phenomenon suggests that the subjective experience of pain is a prerequisite for an inhibitory action. The necessity of using painful stimuli as conditioning and as test stimuli to produce inhibitory effects was investigated in the present study, using a HNCS paradigm. Twenty young men received conditioning stimuli created by tonic heat at painful and non-painful levels, using either hot water (hand) or thermode (forearm). The test stimuli were phasic heat stimuli (thermode) at painful and non-painful levels applied to the cheek. Only painful but not non-painful heat as conditioning stimulus increased the heat pain threshold and decreased the ability to discriminate between painful heat of different intensities. These two findings are in accord with an inhibitory effect depending on a painful conditioning stimulus. However, the intensity ratings of the test stimuli indicated inhibitory effects of the conditioning stimuli also upon non-painful levels. Furthermore, non-painful heat as conditioning stimulus also appeared to be capable of decreasing the ratings of the test stimuli at painful levels. The latter two findings suggest: (i) that very strong but subjectively still non-painful stimulation can trigger pain inhibitory effects and (ii) that also subjectively non-painful stimuli are affected by inhibitory influences during HNCS.     

Heterotopic noxious conditioning stimulation (HNCS) reduced the intensity of spontaneous pain, but not of allodynia in painful peripheral neuropathy.

In 15 patients with painful peripheral neuropathy and dynamic mechanical allodynia, the influence of spontaneous ongoing neuropathic pain on pain sensitivity in a remote pain-free area was examined, as was the influence of ischemia-induced heterotopic noxious conditioning stimulation (HNCS) on the intensity of ongoing pain and brush-evoked allodynia. In addition, the modulating effect of HNCS on pain sensitivity in a pain-free area was investigated. Pain thresholds to pressure and heat as well as the sensitivity to suprathreshold pressure- and heat pain were assessed in the pain-free area. Dynamic mechanical allodynia was induced by a recently developed semi-quantitative brushing technique and the patients continuously rated the intensity of the allodynia using a computerized visual analogue scale (VAS). The total brush-evoked pain intensity was calculated as the area under the VAS curve. At baseline, no significant difference in pain sensitivity was found between patients and their healthy controls in the pain-free area, indicating a lack of activation of pain modulatory systems from the spontaneous pain. Compared to baseline, the patients rated the ongoing neuropathic pain intensity significantly lower during the HNCS-procedure (p<0.05). In contrast, there was no influence from HNCS on the total brush-evoked pain intensity. In the pain-free area higher pressure pain thresholds were demonstrated during conditioning stimulation in patients and controls alike (p<0.01). In controls only, a significantly higher heat pain threshold was found during the HNCS-procedure (p<0.01). The main finding of the present study was that HNCS altered differentially spontaneous and brush-provoked pain in patients with painful peripheral neuropathy.     

fMRI of pain processing in the brain: a within-animal comparative study of BOLD vs. CBV and noxious electrical vs. noxious mechanical stimulation in rat

This study aims to identify fMRI signatures of nociceptive processing in whole brain of anesthetized rats during noxious electrical stimulation (NES) and noxious mechanical stimulation (NMS) of paw. Activation patterns for NES were mapped with blood oxygen level dependent (BOLD) and cerebral blood volume (CBV) fMRI, respectively, to investigate the spatially-dependent hemodynamic responses during nociception processing. A systematic evaluation of fMRI responses to varying frequencies of electrical stimulus was carried out to optimize the NES protocol. Both BOLD and CBV fMRI showed widespread activations, but with different spatial characteristics. While BOLD and CBV showed well-localized activations in ipsilateral dorsal column nucleus, contralateral primary somatosensory cortex (S1), and bilateral caudate putamen (CPu), CBV fMRI showed additional bilateral activations in the regions of pons, midbrain and thalamus compared to BOLD fMRI. CBV fMRI that offers higher sensitivity compared to BOLD was then used to compare the nociception processing during NES and NMS in the same animal. The activations in most regions were similar. In the medulla, however, NES induced a robust activation in the ipsilateral dorsal column nucleus while NMS showed no activation. This study demonstrates that (1) the hemodynamic response to nociception is spatial-dependent; (2) the widespread activations during nociception in CBV fMRI are similar to what have been observed in ¹⁴C-2-deoxyglucose (2DG) autoradiography and PET; (3) the bilateral activations in the brain originate from the divergence of neural responses at supraspinal level; and (4) the similarity of activation patterns suggests that nociceptive processing in rats is similar during NES and NMS.