Identification of genes associated with pain insensitivity syndromes can increase the understanding of the pathways involved in pain and contribute to the understanding of how sensory pathways relate to other neurological functions. In this report we describe the mapping and identification of the gene responsible for loss of deep pain perception in a large family from northern Sweden. The loss of pain perception in this family is characterized by impairment in the sensing of deep pain and temperature but with normal mental abilities and with most other neurological responses intact. A severe reduction of unmyelinated nerve fibers and a moderate loss of thin myelinated nerve fibers are observed in the patients. Thus the cases in this study fall into the class of patients with loss of pain perception with underlying peripheral neuropathy. Clinically they best fit into HSAN V. Using a model of recessive inheritance we identified an 8.3 Mb region on chromosome 1p11.2-p13.2 shared by the affected individuals in the family. Analysis of functional candidate genes in the disease critical region revealed a mutation in the coding region of the nerve growth-factor beta (NGFB) gene specific for the disease haplotype. This NGF mutation seems to separate the effects of NGF involved in development of central nervous system functions such as mental abilities, from those involved in peripheral pain pathways. This mutation could therefore potentially provide an important tool to study different roles of NGF, and of pain control.

An experimental model for inducing chronic Achilles paratenonitis with tendinosis in the rabbit is presented. Thirteen rabbits were exercised in a kicking machine producing passive flexions and extensions of the ankle joint. Active contractions of the triceps surae muscles were induced by electric stimulation via surface electrodes. The animals were exercised for 5 to 6 weeks, with a rate of 150 flexions and extensions per minute for 2 h, three times a week. Light microscopic examination showed degenerative changes of the tendon, and increased number of capillaries, infiltrates of inflammatory cells, edema, and fibrosis in the paratenon. We conclude that chronic Achilles paratenonitis with tendinosis can be experimentally induced in a standardized manner in rabbits.

We performed a prospective study of patients with a whiplash trauma to the cervical spine to describe the incidence of these injuries and to evaluate prognostic factors for disability and recovery. A total of 356 patients were enrolled in the study. All the patients received a comprehensive questionnaire after the injury, and 296 cases responded to the follow-up protocol more than 1 year after the accident. Disability related to the whiplash trauma was used as the outcome variable for the assessment of prognostic factors. The annual incidence of acute whiplash trauma in the catchment area was 4.2 per 1,000 inhabitants and 3.2 per 1,000 for whiplash-associated disorder grades 1-3. Thirty-two percent reported persisting disability at follow-up. The following factors were significantly associated with a poor prognosis: pretraumatic neck pain, low educational level, female gender, and whiplash-associated disorder grades 2-3.

We have studied a large Swedish family with a mutation in the nerve growth factor beta (NGFB) gene causing insensitivity to deep pain without anhidrosis (hereditary sensory and autonomic neuropathy, type V; HSAN V). Painfree joint destruction and fractures were common. Peripheral nerve conduction was normal, but temperature thresholds were increased. Sural nerve biopsies showed a moderate loss of A delta fibers and a severe reduction of C fibers. The three most severely affected cases were all born to consanguineous parents, and were homozygotes for the causal genetic mutation. Treatment of these patients is discussed.

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