Understanding pulpitis

In this issue of The Journal of Physiology, Bletsa et al. (2006) report their findings on the effects of inflammation on the dental pulp. This paper details two important findings: (1) the induction of locally produced cytokines following systemic lipopolysaccharide administration, and (2) the first measurements of pulpal interstitial fluid volume (IFV) and interstitial colloid osmotic pressure (COP), along with the effects of acute pulpal inflammation on these measures. Bletsa et al. report increased pulpal expression, and release into pulpal interstitial fluid, of the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), which was not mirrored by an increase in serum levels of the same cytokines. 'Classical' inflammatory mediators, also released from immune cells, such as prostaglandins, histamine and serotonin, have long been known to act on primary afferents to alter peripheral nociceptive processing (Millan, 1999). Systemic cytokines, including IL-1β and TNF-α, mediate sickness behaviour in inflammation (Dantzer, 2001) and alterations in pain behaviour (Millan, 1999). The latter effect has recently been shown to be distinct from sickness behaviour, and is probably mediated by a peripheral action of IL-1β on vagal sensory afferents (Morgan et al. 2004). Whether local cytokines can activate somatic afferents to produce sickness behaviour without the need for increased circulating levels remains unknown. Both TNF-α and IL-1β exert direct, pro-nociceptive effects on primary afferents, increasing spontaneous activity and lowering nociceptive thresholds, possibly through release of prostaglandins or nerve growth factor (Sorkin et al. 1997; Bianchi et al. 1998). Thus the local production of IL-1β and TNF-α in pulp described by Bletsa et al. probably contributes to the pain of pulpitis by actions on pulpal primary afferent terminals. Net fluid movement across the vessel wall (Jv) is determined by the magnitude of the Starling pressures, the capillary pressure (Pc), the interstitial fluid pressure (IFP) (Pi), the plasma colloid osmotic pressure (COP) (πp), the interstitial COP (πi), the filtration coefficient (Kf) and the reflection coefficient (σ). This latter value can essentially be thought of as the permeability of the capillary wall to plasma proteins, and in most normal tissues lies between 0.75 and 0.98 (Levick, 1991). The values for Starling's forces in dental pulp discussed herein have, in the main, been measured in canine teeth (which have even lower compliance than the rat incisor, which has an open apex) but will still serve to illustrate the principles that may be applied to pulp in general. Normal pulpal blood flow and pulpal capillary pressures are both relatively high (20–60 ml min−1 (100 g pulp)−1 and 35 ± 0.8 mmHg, respectively) (Matthews & Andrew, 1995), and pulpal IFP, in contrast to most other tissues, is well above atmospheric pressure (6–60 mmHg) (Heyeraas & Berggreen, 1999). The finding of Bletsa et al. (2006) that pulpal COP (πi) was 19.6 ± 1.3 mmHg, being 83% of plasma COP (πp) is unexpected, and gives valuable information on the normal function of pulpal capillaries. This is one of the highest values of interstitial COP reported. Rat incisal pulp has fenestrated and continuous capillaries (Ohshima & Yoshida, 1992). In tissues with these types of capillaries, πi/πp ratios are typically between 0.3 and 0.6. Higher values are usually only found in tissues with discontinuous capillary beds such as the liver (Levick, 1991). Under steady state filtration, the reflection coefficient approximates to 1 − (πi/πp) and this therefore implies that the normal permeability of pulpal vessels to plasma proteins is very high (σ≈ 0.17). Capillary density in pulp is high and flow rate is low; combined with the observations above, this shows that filtration in the pulp must be very high under normal conditions, giving a high pulpal IFV, as reported by Bletsa et al. In addition, due to the high pulpal COP, the net filtration pressure in the whole vascular bed must be outwards, and there is not, under normal circumstances, absorption of tissue fluid into pulpal postcapillary venules. In low compliance systems such as dental pulp, alterations in capillary filtration, such as in inflammation, can have dramatic effects. Undergraduate dental students are still often mistaught that pulpal necrosis occurs as a result of self-strangulation of pulpal venules due to increased filtration and increased intrapulpal pressure. It has also been proposed that pulpal inflammation does not lead to strangulation and necrosis because the increased pressure in an area of inflammation is transmitted to non-inflamed areas, where excess interstitial fluid is reabsorbed into the venules (Tonder, 1983). During inflammation, the IFP of dental pulp rises approximately threefold (Heyeraas & Berggreen, 1999), but Bletsa et al. (2006) have shown that incisal vascular fluid volume does not change and pulpal blood flow falls on LPS administration. Thus in inflammation, pulpal vessels are not compressed to the point of closure, but rather, as blood flow falls, postcapillary resistance is increased. Under these conditions, πi/πp is essentially unity and pulpal IFV does not change. The equilibration of protein concentration across the vessel walls implies that permeability of the vessels has increased. For reabsorption to occur under these conditions, the postcapillary venular pressure must fall below the IFP; however, if this occurs, the raised IFP will further compress the venules, increasing postcapillary resistance and hence capillary pressure, until filtration begins again, but with a reduced blood flow due to reduced arterio-venular pressure difference. Pulpal inflammation therefore increases filtration leading to excess tissue fluid accumulation which cannot be countered by sustained absorption into venules even in uninflamed areas, but must be drained by the lymphatics. Tissue therefore must become compromised and necrotic when lymphatic drainage cannot match filtration and IFP increases to the point where blood flow is reduced to a level where oxygen delivery to the pulp is insufficient. How pulpal lymphatic drainage may be altered in inflammation remains a missing piece in the puzzle of pulpitis. These important findings relating to the main sequelae of pulpal inflammation, namely pain and the vascular events that may lead to pulpal necrosis, contribute greatly to our understanding of pulpal physiology and pathology.