There are no satisfactory animal models of trigeminal neuralgia, and it is difficult to obtain essential data from patients. However, trigeminal neuralgia presents with such idiosyncratic signs and symptoms, and responds to so distinctive a set of therapeutic modalities, that scientific deduction can be used to generate likely hypotheses. The ignition hypothesis of trigeminal neuralgia is based on recent advances in the understanding of abnormal electrical behavior in injured sensory neurons, and new histopathologic observations of biopsy specimens from patients with trigeminal neuralgia who are undergoing microvascular decompression surgery. According to the hypothesis, trigeminal neuralgia results from specific abnormalities of trigeminal afferent neurons in the trigeminal root or ganglion. Injury renders axons and axotomized somata hyperexcitable. The hyperexcitable afferents, in turn, give rise to pain paroxysms as a result of synchronized afterdischarge activity. The ignition hypothesis accounts for the major positive and negative signs and symptoms of trigeminal neuralgia, for its pathogenesis, and for the efficacy of treatment modalities. Proof, however, awaits the availability of key experimental data that can only be obtained from patients with trigeminal neuralgia.

Findings were consistent with the ignition hypothesis of TN. This model can be used to explain the major positive and negative symptoms of TN by axonopathy-induced changes in the electrical excitability of afferent axons in the trigeminal root and of neuronal somata in the trigeminal ganglion. The key pathophysiological changes include ectopic impulse discharge, spontaneous and triggered afterdischarge, and crossexcitation among neighboring afferents.

Idiosyncrasies of trigeminal neuralgia provide both clues and constraints on candidate hypotheses concerning the underlying neural mechanism. After reviewing the key clinical aspects of the disease, we propose here a novel hypothesis based on recent findings from experimental nerve-injury preparations. The hypothesis states that trigger stimuli set off bursts of activity in a small cluster of trigeminal ganglion (TRG) neurons that have been rendered hyperexcitable as a result of TRG or trigeminal root damage. Activity then spreads from this "TRG ignition focus" to encompass more widespread portions of the ganglion. After a brief period of autonomous firing (seconds to minutes), activity is quenched and a refractory period is initiated by an intrinsic suppressive (hyperpolarizing) process engaged as a result of the rapid firing. The primary abnormality resides in the TRG and trigeminal root, rather than in the skin or the CNS. Because of this, sensation is essentially normal between periods of ectopic paroxysmal TRG discharge.

Middle cerebral artery occlusions (MCAo) in rats produce infarcts in the pyriform and frontoparietal cortex, extending into the lateral basal ganglia and parasagittal cortex. We estimated tissue H 2 O concentrations from wet and dry weight measurements and determined Na and K concentrations by atomic absorption spectroscopy in these areas of rat brains. Tissue samples were analyzed at 2,4, and 24 hours after MCAo and sham MCAo, compared with normal values measured in unoperated rats. In the pyriform and frontoparietal areas, H 2 O concentrations increased to 34 and 7% greater than normal by 2 hours, and 89 and 94% by 24 hours after MCAo. Na concentrations rose in these areas to 73 and 37% greater than normal by 2 hours, and 281 and 330% by 24 hours. K concentrations did not change until 4 hours, but fell to 62 and 34% of normal in these areas by 24 hours. Such large ion shifts indicate severe tissue destruction. In the parasagittal cortex and basal ganglia areas, the ion and water changes were smaller and did not become significant until 24 hours after MCAo. Rates of Na entry into the infarct site were greatest at 0-2 hours, while the rates of K loss peaked later, between 2 and 4 hours. The difference in Na influx and K efflux resulted in net ion shifts that correlated highly with water entry, yielding a correlation coefficient of 0.992 (p < 0.001) and a slope indicating that 1 ml of water entered the tissue with each 145 /xmoles of ions. These findings strongly suggest that net ion shifts cause the early edema of regional brain ischemia. To explain the dominance of Na gain over K loss, we reject the hypothesis of a selective increase of blood-brain barrier Na permeability and propose instead that glial buffering of K ions released by Ischemic neurons reduced the driving force for K clearance during the first 2-4 hours after MCAo. (Stroke 1987;18:751-759) T he middle cerebral artery (MCA) occlusion (MCAo) model in rats possesses several major advantages over other models of cerebral ischemia. First, unlike global ischemia models, 1 " 3 occlusion of cerebral arteries produces regional losses of blood flow, allowing ischemic sites to be compared with perfused tissues in the same brain. Second, the effects of severe ischemia can be investigated in animals with relatively low mortality rates. Third, unlike MCAo models in larger mammals such as cats and primates, rats can be studied in large numbers.In an earlier study, 4 we showed that tissue ion shifts in injured spinal cords can serve as quantitative indices of the severity and time course of cell damage. Here, a similar approach was applied to the rat MCAo model of regional ischemia. The time course and regional distribution of Na, K, and water changes at 2, 4, and 24 hours after unilateral MCAo were compared with measurements in sham-occluded and unoperated rats. We report below earlier and larger changes in brain Na, K, and water shifts than described previously. Received April 1, 1986; accepted February 6, 1987. Na influx exceeded K efflux, resulting in ...

Dexanabinol was safe and well tolerated in severe head injury. The treated patients achieved significantly better intracranial pressure/cerebral perfusion pressure control without jeopardizing blood pressure. A trend toward faster and better neurologic outcome was also observed.