Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1.

Not all patients with nerve injury develop neuropathic pain. The extent of nerve damage and age at the time of injury are two of the few risk factors identified to date. In addition, preclinical studies show that neuropathic pain variance is heritable. To define such factors further, we performed a large-scale gene profiling experiment which plotted global expression changes in the rat dorsal root ganglion in three peripheral neuropathic pain models. This resulted in the discovery that the potassium channel alpha subunit KCNS1, involved in neuronal excitability, is constitutively expressed in sensory neurons and markedly downregulated following nerve injury. KCNS1 was then characterized by an unbiased network analysis as a putative pain gene, a result confirmed by single nucleotide polymorphism association studies in humans. A common amino acid changing allele, the 'valine risk allele', was significantly associated with higher pain scores in five of six independent patient cohorts assayed (total of 1359 subjects). Risk allele prevalence is high, with 18-22% of the population homozygous, and an additional 50% heterozygous. At lower levels of nerve damage (lumbar back pain with disc herniation) association with greater pain outcome in homozygote patients is P = 0.003, increasing to P = 0.0001 for higher levels of nerve injury (limb amputation). The combined P-value for pain association in all six cohorts tested is 1.14 E-08. The risk profile of this marker is additive: two copies confer the most, one intermediate and none the least risk. Relative degrees of enhanced risk vary between cohorts, but for patients with lumbar back pain, they range between 2- and 3-fold. Although work still remains to define the potential role of this protein in the pathogenic process, here we present the KCNS1 allele rs734784 as one of the first prognostic indicators of chronic pain risk. Screening for this allele could help define those individuals prone to a transition to persistent pain, and thus requiring therapeutic strategies or lifestyle changes that minimize nerve injury.

Development of palliative care in Israel and the rising status of the clinical nurse specialist.

It was in 2009 that the Ministry of Health in Israel issued unique recognition for registered nurses. Palliative Care has been recognized as a specialty for nurses, working already in different clinical specialties. By obtaining the qualification of a Clinical Nurse Specialist in Palliative Care, nurses obtained the de jure status of what they have been doing for years de facto.

Involvement of the family physician in the care of chemotherapy-treated patients with cancer: patients' perspectives.

PURPOSE: Increasing numbers of patients receive active ambulatory oncology treatment over prolonged periods of time. Many of these patients suffer from additional comorbidities and require comprehensive medical care. We aimed to assess the perception of patients with cancer regarding the role of the family physician and the oncologist in their care during times of active cancer treatment. PATIENTS AND METHODS: A survey was conducted among 265 consecutive chemotherapy-treated patients at the daycare oncology clinic. RESULTS: All the patients were affiliated with one of four Israeli health maintenance organizations, 96% had a regular family physician, and 70% had met with him during the preceding month. Only one third of the patients thought their family physician was trained to or was willing to treat medical problems that occurred during chemotherapy treatment. Yet most patients, irrespective of clinical or socioeconomic variables, stated that involvement of the family physician was important to them. Only 30% stated that the oncologist communicated with the family physician. Accordingly, 72% of the patients stated that in the case of an urgent problem they would turn first to the oncology clinic; only 9% would consult their family physician. CONCLUSIONS: Our data point to a lack of communication between team members and inadequate medical training as major barriers for comprehensive medical care for chemotherapy-treated patients with cancer. Communication between treating teams may improve medical care for oncology patients with multiple treating practitioners.

Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity.

Chronic pain is highly variable between individuals, as is the response to analgesics. Although much of the variability in chronic pain and analgesic response is heritable, an understanding of the genetic determinants underlying this variability is rudimentary. Here we show that variation within the coding sequence of the gene encoding the P2X7 receptor (P2X7R) affects chronic pain sensitivity in both mice and humans. P2X7Rs, which are members of the family of ionotropic ATP-gated receptors, have two distinct modes of function: they can function through their intrinsic cationic channel or by forming nonselective pores that are permeable to molecules with a mass of up to 900 Da. Using genome-wide linkage analyses, we discovered an association between nerve-injury-induced pain behavior (mechanical allodynia) and the P451L mutation of the mouse P2rx7 gene, such that mice in which P2X7Rs have impaired pore formation as a result of this mutation showed less allodynia than mice with the pore-forming P2rx7 allele. Administration of a peptide corresponding to the P2X7R C-terminal domain, which blocked pore formation but not cation channel activity, selectively reduced nerve injury and inflammatory allodynia only in mice with the pore-forming P2rx7 allele. Moreover, in two independent human chronic pain cohorts, a cohort with pain after mastectomy and a cohort with osteoarthritis, we observed a genetic association between lower pain intensity and the hypofunctional His270 (rs7958311) allele of P2RX7. Our findings suggest that selectively targeting P2X7R pore formation may be a new strategy for individualizing the treatment of chronic pain.