Ectopic discharge originating from the ostium of the inferior vena cava that is likely to cause atrial fibrillation.

It has been established that the initiation of paroxysmal atrial fibrillation (AF) is frequently associated with ectopic beats inside the thoracic veins, including the pulmonary veins, superior vena cava, coronary sinus, and/or vein of Marshall. However, similar arrhythmogenic ectopic discharge or premature atrial contractions (PACs) originating from the inferior vena cava (IVC) have been rarely described. We present the case of a 51-year-old man with paroxysmal AF undergoing electrophysiological study. Twelve-lead electrocardiography demonstrated PACs with negative P waves in the inferior leads. Ectopic beats originating from the ostium of the IVC, which were likely to initiate AF, were observed. Furthermore, the origin of the PAC was visualized using an electroanatomical local activation timing (LAT) map and located close to the fibrotic tissue of the vasculature. Radiofrequency catheter ablation was performed at the earliest activation site, and ectopic beats were not observed after the procedure. This is the first report to demonstrate a LAT contact map of ectopic discharge arising from the IVC. If PACs with negative P waves in the inferior leads are found in a patient with AF, the IVC should be investigated for possible focal ectopic discharges. Learning objective: Non-pulmonary vein foci play a significant role in the pathogenesis of atrial fibrillation (AF). However, inferior vena cava (IVC) triggers that initiate AF have rarely been described. Premature atrial contractions with negative P waves in the inferior leads may be associated with ectopic discharges originating from the IVC, which contribute to the initiation of AF.

Rethinking the causes of pain in herpes zoster and postherpetic neuralgia: the ectopic pacemaker hypothesis.

INTRODUCTION: Pain in herpes zoster (HZ) and postherpetic neuralgia (PHN) is traditionally explained in terms of 2 processes: irritable nociceptors in the rash-inflamed skin and, later, deafferentation due to destruction of sensory neurons in one virally infected dorsal root ganglion. OBJECTIVES AND METHODS: Consideration of the evidence supporting this explanation in light of contemporary understanding of the pain system finds it wanting. An alternative hypothesis is proposed as a replacement. RESULTS: This model, the ectopic pacemaker hypothesis of HZ and PHN, proposes that pain in both conditions is driven by hyperexcitable ectopic pacemaker sites at various locations in primary sensory neurons affected by the causative varicella zoster virus infection. This peripheral input is exacerbated by central sensitization induced and maintained by the ectopic activity. CONCLUSIONS: The shift in perspective regarding the pain mechanism in HZ/PHN has specific implications for clinical management.

Effect and Mechanism of Dexmedetomidine Hydrochloride on Neuropathic Pain / 医药导报

Objective To establish neuropathic pain models,explore the effects and mechanisms of dexmedetomidine on neuropathic pain.Methods Wistar rats were randomly divided into four groups (n =9):0.9％ sodium chloride solution CCI group (N),dexmedetomidine CCI group (D),ZD7288 CCI group (Z) and sham-operated group (Sham).Sciatic nerve ligation was performed in group N,D and Z.The sciatic nerve in group Sham was exposured without ligation.7 d after surgery,the rats in group D were intraperitoneal injected with dexmedetomidine (40 μg· kg-1),and the rats in group Z were intraperitoneal injected with ZD7288 (10 mg·kg-1)once a day for 3 d.The same volume of 0.9％ sodium chloride solution was given at the same time in group N.The behavioral test was performed before and 7 d after operation,as well as 3 d after injection treatment.Mechanical allodynia was assessed by paw withdrawal mechanical threshold (PWMT) to von Frey filaments.Thermal hyperalgesia was assessed by paw thermal withdrawal latency (TWL) to radiant heat.Dexmedetomidine block of HCN channels in dorsal root ganglion (DRG) neurons were confirmed by whole-cell recording.Results 7 d after surgery,the PWMT and TWL of rats in group N,D and Z were decreased significantly (P ＜ 0.05).The PWMT and TWL in group Sham were no significant difference before and after operation.Dexmedetomidine significantly increased the levers of PWMT and TWL in group D and Z after treatment for 3 d,and group Z was greater than group D (P ＜ 0.05).Dexmedetomidine (0.1,1,10 μmol· L-1) caused a concentration-dependent decrease in the amplitude of Ih in DRG neurons from (-844.43 ± 386.34) to (-215.99 ± 63.90) pA (P ＜ 0.05),and the inhibition rate of Ih was (11.87 ± 1.80) ％,(35.26 ± 3.65) ％ and (52.02 ± 5.56) ％,respectively(P ＜0.05).Dexmedetomidine produced a dose-related shift to the left of the Ih activation,and a negative shift in V1/2 (P ＜ 0.05).V1/2 shifted from (-86.21 ± 1.68) to (-103.54 ± 2.01) mV (P ＜ 0.05).The slope values were not altered by dexmedetomidine.Conclusion Dexmedetomidine produces a dose-dependently analgesic effect on neuropathic pain after peripheral never injury,which is likely due to the inhibition of Ih and reduction of ectopic spontaneous discharge in DRG neurons.

Neuropathic Pain: Sensory Nerve Injury or Motor Nerve Injury?

Peripheral nerve injury often induces chronic neuropathic pain. Peripheral nerve is consisted of sensory fibers and motor fibers, it is questioned injury to which type of fibers is responsible for generation of neuropathic pain? Because neuropathic pain is sensory disorder, it is generally believed that the disease should be induced by injury to sensory fibers. In recent years, however, emergent evidence shows that motor fiber injury but not sensory fiber injury is necessary and sufficient for induction of neuropathic pain. Motor fiber injury leads to neuropathic pain by upregulating pro-inflammatory cytokines and brain-derived neurotrophic factor in pain pathway.

In vivo electrophysiological recording techniques for the study of neuropathic pain in rodent models.

Neuropathic pain develops following nerve injury, and is a chronic pain syndrome that can persist long after repair of a wound or removal of the neurological insult. This condition remains poorly treated, not least because of a lack of mechanism-based therapeutics. Clinically, neuropathic pain is characterized by three major symptoms: thermal or mechanical allodynia (pain sensation in response to previously non-noxious stimuli); hyperalgesia (enhanced pain sensation to noxious stimulation); and spontaneous, ongoing pain. These clinical symptoms can be modeled in rodent neuropathic pain models using behavioral and electrophysiological readouts. This unit describes techniques designed to record pathophysiological electrical activity associated with neuropathic pain at the level of the periphery, in single fibers of primary sensory neurons, and from wide dynamic range (WDR) neurons of the dorsal horn of the spinal cord. These techniques can be employed in both naïve animals and in animal models of neuropathy to investigate fundamental mechanisms contributing to the neuropathic pain state and the site, mode, and mechanism of action of putative analgesics.