Pain Part 5b: Non-Odontogenic Dysfunctional Pain.

UNLABELLED: Orofacial chronic pain provides a significant challenge to all clinicians and the patients seeking treatment for it. Due to the anatomical and regional complexities, diagnosis can be extremely difficult, and due to the lack of cross specialty training, patients will undergo a variety of treatment under different disciplines. Dysfunctional pain provides a unique challenge for patient management and requires a multidisciplinary team. CLINICAL RELEVANCE: Lack of recognition of dysfunctional chronic pain can result in inappropriate dental treatment and further damage. to the patient. Appropriate patient reassurance and referral to an orofacial pain multidisciplinary team is recommended as most of these conditions require medical management.

Pain. Part 2a: Trigeminal Anatomy Related to Pain.

In order to understand the underlying principles of orofacial pain it is important to understand the corresponding anatomy and mechanisms. Paper 1 of this series explains the central nervous and peripheral nervous systems relating to pain. The trigeminal nerve is the 'great protector' of the most important region of our body. It is the largest sensory nerve of the body and over half of the sensory cortex is responsive to any stimulation within this system. This nerve is the main sensory system of the branchial arches and underpins the protection of the brain, sight, smell, airway, hearing and taste, underpinning our very existence. The brain reaction to pain within the trigeminal system has a significant and larger reaction to the threat of, and actual, pain compared with other sensory nerves. We are physiologically wired to run when threatened with pain in the trigeminal region and it is a 'miracle' that patients volunteer to sit in a dental chair and undergo dental treatment. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the trigeminal anatomy of pain and the principles of pain assessment.

Pain paper 2b: classification of orofacial pain and an update on assessment and diagnosis.

The classification of chronic orofacial pain remains a contentious area. However, more recently, with the clarification of pain mechanisms and improved understanding of the underlying neurophysiology and modulation factors, there is more clarity of the possible division of pain conditions. Interestingly, the pathophysiology provides a basis for classification that has more clinical relevance. The principles of assessing and managing patients with pain have modified significantly, in line with recent improved understanding of the affective and emotional components in pain behaviour and suffering. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the classification of trigeminal pain with an overview of how to assess and diagnose patients with trigeminal pain.

Phenotype-independent effects of retroviral transduction in human dental pulp stem cells.

An immortalized human dental pulp stem cell (DPSC) line of an odontoblastic phenotype is established to circumvent the normal programmed senescence and to maintain the cell line's usefulness as a tool for further study of cellular activity. DPSCs are isolated from human dental pulp tissues and transfected using hTERT. The influence of this process on the DPSC phenotype and the mRNA expression of oncogenes involved in cellular senescence is investigated. The results reveal an absence of altered DPSC morphology and phenotype following the exogenous introduction of the hTERT gene, which is coupled with a significant reduction in p16 mRNA expression. This provides insight into how to circumvent in vitro dental pulp stem cell death following the exogenous introduction of hTERT.

P16/p53 expression and telomerase activity in immortalized human dental pulp cells.

INTRODUCTION: Residing within human dental pulp are cells of an ectomesenchymal origin which have the potential to differentiate into odontoblast-like cells. These cells have a limited growth potential owing to the effects of cell senescence. This study examines the effects of immortalizing odontoblast-like cells on cell proliferation and mineralization by comparing transformed dental pulp stem cells (tDPSCs) and non-transformed dental pulp stem cells (nDPSCs). RESULTS: With the exogenous expression of hTERT, tDPSCs maintained a continued expression of odontogenic markers for cell proliferation and mineralization (ALP, COL-1, DMP-1, DSPP, OCN amd OPN)as did nDPScs. Oncoprotein expression was seen in both groups except for a noted absence of p16 in the tDPSCs. nDPSCs also showed lower levels of total ALP and DNA activity in comparison to tDPSCs when assayed as well as low telomerase activity readings. METHODS: Using a retroviral vector, exogenous human telomerase reverse transcriptase (hTERT) was expressed in tDPSCs. Both cell groups were cultured and their telomerase activities is determined using a telomerase quantification assay. Also examined were the expression of genes involved in proliferation and mineralization such as human alkaline phosphatase (ALP), ß-actin, collagen 1 (col-1), core binding factor (cbfa-1), dentin matrix protein (DMP-1), dentin sialophosphoprotein (DSPP), GAPDH, hTERT, osteocalcin (OCN), osteopontin (OPN) as well as oncoproteins involved in senescence (p16, p21 and p53) using RT-PCR. DNA and alkaline phosphatase activity was assayed in both cell groups. CONCLUSIONS: These results indicate maintainance of odontoblast-like differentiation characteristics after retroviral transformation with hTERT and suggest a possible link with a reduced p16 expression.