Depression-like behaviour in rats with mononeuropathy is reduced by the CB2-selective agonist GW405833

The current study assessed whether the chronic constriction injury (CCI) model of neuropathic pain causes depression-like behaviour in animals, and if this depression-like behaviour can be reversed by anti-nociceptive and/or antidepressant drugs. CCI of the sciatic nerve in rats was selected as a neuropathic pain model, mechanical hypersensitivity was assessed by punctuate mechanical stimuli, and depression-like behaviour was evaluated in the forced swimming test (FST) measuring the time of immobility, climbing and swimming. The CCI rats displayed a significant mechanical hypersensitivity (sham 27 ± 2 g, CCI 12 ± 2 g; P < 0.001) and a significant increase in time of immobility (sham 133 ± 14 s, CCI 201 ± 9 s; P < 0.001). As time of swimming was unchanged, immobility was increased at the expense of climbing behaviour (sham 105 ± 17 s, CCI 63 ± 9 s; P < 0.05). There was no difference in ambulation between sham and CCI animals. In sham and CCI animals, desipramine (20 mg/kg) significantly reduced immobility (sham + vehicle 134 ± 19 s, sham + desipramine 79 ± 13 s; P < 0.01, CCI + vehicle 195 ± 8 s, CCI + desipramine 140 ± 11 s; P < 0.05) and increased climbing behaviour (sham + vehicle 118 ± 21 s, sham + desipramine 182 ± 16 s; P < 0.05, CCI + vehicle 59 ± 8 s, CCI + desipramine 112 ± 14 s; P < 0.05) with little effect on mechanical hypersensitivity. In contrast in CCI animals the cannabinoid CB2-selective agonist GW405833 (2,3-dichloro-phenyl)-[5-methoxy-2-methyl-3-(2-morpholin-4-yl-ethyl)-indol-1-yl]-methanone) (30 mg/kg) significantly attenuated immobility (CCI + vehicle 191 ± 7 s, GW405833 145 ± 14 s; P < 0.01) and mechanical hypersensitivity (CCI + vehicle 15 ± 1 g, CCI + GW405833 24 ± 1 g; P < 0.001). Moreover, differently from desipramine, GW405833 did not change the climbing behaviour. These data suggest that rats subjected to the CCI model of neuropathic pain develop depression-like behaviour, which can be reversed by appropriate anti-nociceptive treatment.     

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes

Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli.     

Zertifizierungsrichtlinien für QST-Labore

Quantitative sensory testing (QST) is the standardized assessment of the somatosensory system comprising all sensory submodalities. In the German Research Network on Neuropathic Pain (DFNS), a QST-battery consisting of 13 parameters has been established and nationwide normative data have been collected. In contrast to conventional electrophysiology, QST allows detecting negative and positive sensory signs of both large and small fiber systems. However, as a subjective psychophysical method it is critically dependent on patients’ / healthy subjects’ cooperation thus strictly standardized protocols and instructions are needed to allow across laboratory comparisons. To facilitate more widespread use of QST, the German Pain Society (DGSS) and the DFNS have initiated a certification procedure for QST quality standards. Therefore, structural, procedural criteria and outcome parameters were establishd and are hereby presented. By maintaining high quality standards, the certification of QST is intended to contribute to a better understanding of the mechanisms behind neuropathic pain syndromes and thereby improve patient care as well as sensory assessment in clinical studies on the treatment of neuropathic pain syndromes.     

Abolished laser-evoked potentials and normal blink reflex in midlateral medullary infarction

We investigated two patients presenting with the rare finding of almost isolated hemianalgesia with a sensory level on the contralateral side sparing the face. Clinical findings, electrophysiological studies (absent laser-evoked pain-related somatosensory potentials, normal electrically evoked somatosensory potentials, magnetically evoked potentials, and blink reflexes), and magnetic resonance imaging showed the ventrolateral medullar tegmentum containing the spinothalamic tract to be affected by lacunar infarction. The blink reflex R2 component was unimpaired in both patients. Received: 7 May 1998 Received in revised form: 21 July 1998 Accepted: 26 August 1998     

C- and A delta-fiber components of heat-evoked cerebral potentials in healthy human subjects.

Feedback-controlled laser heat was used to stimulate the hairy skin of the hand dorsum and forearm, and heat-evoked cerebral potentials were recorded at midline (Fz, Cz, Pz) and temporal (T3, T4) scalp positions. Based on data from primary afferent electrophysiology a stimulus level (40 degrees C) was chosen, which is above C-fiber heat threshold, but clearly below A delta-nociceptor heat threshold in order to excite selectively C-fibers without concomitant excitation of A delta-fibers. Feedback-controlled stepped heat stimuli to 40 degrees C elicited ultralate laser evoked potentials (LEPs) at the vertex in a high proportion of experiments (90%). Estimates of conduction velocity calculated from latency shifts between the hand and forearm sites of ultralate LEPs (2.4 m/s) and of reaction times (2.8 m/s) confirmed mediation of ultralate potentials by unmyelinated nerve fibers (nociceptors and/or warm fibers). The ultralate LEP could be differentiated from resolution of contingent negative variation (CNV), an endogenous potential related to expectation and response preparation, by its scalp topography. Strong heat stimuli of 48 degrees C, which is suprathreshold for most A delta- and C-fiber nociceptors, elicited the well-known late LEPs mediated by nociceptive Adelta-fibers confirming previous studies. The LEP waveform to strong heat stimuli also contained an ultralate component reminiscent of an ultralate LEP following the late LEP. Ultralate and late LEP had identical scalp topography. In conclusion, the method of temperature-controlled laser heat stimuli allows the selective and reliable examination of A delta- and C-fiber-mediated afferent pathways and the related cortical processing without the complication of dissociating A-fiber nerve blocks.     

Depression and changed pain perception: hints for a central disinhibition mechanism

Although patients with a depressive disorder report often of pain, their sensitivity to experimental pain is controversial, probably due to differences in sensory testing methods and to the lack of normal values. Therefore, we used a standardized and validated comprehensive sensory testing paradigm to assess the peripheral and central nervous system performance in depressive patients compared to healthy controls and chronic pain patients with fibromyalgia syndrome (FMS), in which depression is a common comorbidity. Twenty-five depressive psychiatric inpatients (pain-free: n=20), 35 FMS outpatients and 25 healthy controls underwent quantitative sensory testing (QST), including thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimuli (wind-up). In depressive disorder (to a lesser extent also in FMS), significantly decreased cold pain thresholds and an increased wind-up were found, although the mechanical pain thresholds and pain sensitivity were comparable to those of the healthy controls. All the detection thresholds were within the normal range in all the groups. In depressive disorder, there were no significant side differences in the detection and pain thresholds. The results contradict the former assumption of a general insensitivity to experimental pain in depressive disorder. In the mostly pain-free patients signs of an enhanced central hyperexcitability are even more pronounced than usually found in chronic pain patients (e.g. FMS), indicating common mechanisms in depressive disorder and chronic pain in accordance with the assumption of non-pain associated mechanisms in depressive disorder for central hyperexcitability, e.g. by inhibited serotonergic function. Furthermore, this trial demonstrates the feasibility of QST in depressive patients.