Otorhinolaryngological patient injuries in Finland.

OBJECTIVES/HYPOTHESIS: Otorhinolaryngology (ORL) is considered a specialty associated with few serious patient injuries. Research data that support this belief are, however, scarce. We analyzed claims associated with ORL to determine the number of Finnish cases and the possible common denominators. STUDY DESIGN: Register study of ORL cases in the Patient Insurance Centre (PIC), the Regional State Administrative Agencies (RSAA), and the National Supervisory Authority for Welfare and Care (Valvira) during the years 2004 to 2008. METHODS: These three agencies are the main actors in the field of patient injury in Finland. We analyzed compensated ORL patient injury cases from the PIC and cases associated with the ORL specialty for Valvira and RSAA from 2004 to 2008 and surveyed patient treatment files, statements from specialists, and compensation decisions. RESULTS: Injuries were usually associated with operations; three patients who experienced injuries during these procedures died. Common ORL operations such as tonsillectomy, septoplasty, and paranasal sinus surgery were most often associated with compensated injuries. Serious injuries were few, with a total of 110 out of 422 (26.1%) claims compensated by the PIC. Of the 110 compensated cases, 30 (27.3%) were related to tumor surgery. The most usual compensated case had iatrogenic nerve injury affecting the facial or trigeminal nerves. Of the compensated cases, 79 (71.8%) were treated by specialists, 15 (13.6%) by residents, and the rest by other medical professionals. CONCLUSIONS: Patient injuries in ORL are seldom severe and are strongly associated with surgery. A typical compensated injury was one that occurred in a central hospital during working hours. LEVEL OF EVIDENCE: N/A.

The contribution of autophosphorylated alpha-calcium-calmodulin kinase II to injury-induced persistent pain.

Increases in neuronal activity in response to tissue or nerve injury can lead to prolonged functional changes in the spinal cord resulting in an enhancement/sensitization of nociceptive processing. To assess the contribution of alpha-calcium-calmodulin kinase II (alpha-CaMKII) to injury-induced inflammation and pain, we evaluated nociceptive responses in mice that carry a point mutation in the alpha-CaMKII gene at position 286 (threonine to alanine). The mutated protein is unable to autophosphorylate and thus cannot function independently of calcium and calmodulin. Responses to acute noxious stimuli did not differ between alpha-CaMKII T286A mutant and wild type mice. However, the ongoing pain produced by formalin injury was significantly reduced in the mutant mice, as was formalin-evoked spinal Fos-immunoreactivity. In contrast, the decreased mechanical and thermal thresholds associated with nerve injury, Complete Freund's Adjuvant-induced inflammation or formalin-evoked tissue injury were manifest equally in wild-type and mutant mice. Double-labeling immunofluorescence studies revealed that in the mouse alpha-CaMKII is expressed in the superficial dorsal horn as well as in a population of small diameter primary afferent neurons. In summary, our results suggest that alpha-CaMKII, perhaps secondary to an N-methyl-D-aspartate-mediated calcium increase in postsynaptic dorsal horn nociresponsive neurons, is a critical contributor to the spontaneous/ongoing component of tissue-injury evoked persistent pain.

Nerve injury-induced pain in the trigeminal system.

This article reviews some recent findings on peripheral mechanisms related to the development of oro-facial pain after trigeminal nerve injury. Chronic injury-induced oro-facial pain is not in itself a life-threatening condition, but patients suffering from this disorder undoubtedly have a reduced quality of life. The vast majority of the work on pain mechanisms has been carried out in spinal nerve systems. Those studies have provided great insight into mechanisms of neuropathic spinal pain, and much of the data from them is obviously relevant to studies of trigeminal pain. However, it is now clear that the pathophysiology of the trigeminal nerve (a cranial nerve) is in many ways different to that found in spinal nerves. Whereas some of the changes seen in animal models of trigeminal nerve injury mimic those occurring after spinal nerve injury (e.g., the development of spontaneous activity from the damaged axons), others are different, such as the time-course of the spontaneous activity, some of the neuropeptide changes in the trigeminal ganglion, and the lack of sprouting of sympathetic terminals in the ganglion. Recent findings provide new insights that help our understanding of the etiology of chronic injury-induced oro-facial pain. Future investigations will hopefully explain how data gained from these studies relate to clinical pain experience in man and should enable the rapid development of new therapeutic regimes.

Neuropeptide Y in trigeminal ganglion following chronic constriction injury of the rat infraorbital nerve: is there correlation to somatosensory parameters?

The aim of this study was to investigate neuropeptide Y (NPY) levels in trigeminal ganglia following infraorbital nerve injury. Two experimental procedures were performed in three groups of rats: a unilateral chronic constriction injury (CCI) to the infraorbital nerve (n=13), nerve manipulation without CCI (n=13) and unoperated controls (n=8). All rats underwent baseline and regular assessment of mechanical withdrawal threshold (Von Frey) and reaction to pin prick as well as free behavior evaluations. CCI to the infraorbital nerve induced significant hyperalgesia and allodynia within 9-12 days. At 6 days seven rats were euthanized and trigeminal ganglia harvested for immunocytochemical (ICC) studies. The study was ended at 14 days when all rats were euthanized and their ganglia harvested for ICC and radioimmunoassay (RIA) studies. An increase in NPY levels was seen in the ipsilateral ganglia of manipulated and CCI rats at 6 days, when rats displayed no pain-related behavior. At 14 days, ICC and RIA both detected significant increases in NPY levels in the ipsilateral ganglia of CCI and manipulated rats but not in unoperated controls. The possible roles of NPY in pain modulation and nerve injury are discussed in light of these findings.

Establishment of latent ganglionic infection with herpes simplex virus via maxillary gingiva and viral re-activation in vivo after trauma.

Herpes simplex virus can remain latent for months or years in sensory and automatic ganglia of animals and man, and can be re-activated in vivo by several procedures such as neurectomy, irritation of epithelial surfaces, and administration of immunosuppressive agents. The objective of this study was to determine whether dental stimuli can cause re-activation of the latent herpes simplex virus. Homogenization and explanation of ganglia from mice showed that herpes simplex virus (type 1) traveled from maxillary gingiva to trigeminal ganglia, and remained latent. It was also shown that mice passively immunized with rabbit antibody to herpes simplex virus, following the inoculation of herpes simplex virus by the maxillary gingiva route, developed a latent infection in the trigeminal ganglia. Neutralizing antibody was cleared from the circulation and could not be detected in most of these animals after five weeks. A neutralizing test showed that antibody-negative mice with latent infection were able to produce antibody to re-infection with herpes simplex virus, suggesting that re-activation can be identified by measurement of serum antibody. By use of this mouse model system, it was shown that when maxillary gingiva was traumatized with dry ice, viral re-activation occurred in 58% of these animals, as demonstrated by the appearance of neutralizing antibody. Irradiation by a Stomalaser beam had no effect on the re-activation of latent herpes simplex virus. Our mouse model system may serve as a useful model for obtaining new information on re-activating or inhibitory factors in dentistry.