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This Article Abstract Full Text (PDF) All Versions of this Article: 293/1/H784    most recent 00323.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Hodges, G. J. Articles by Johnson, J. M. Search for Related Content PubMed PubMed Citation Articles by Hodges, G. J. Articles by Johnson, J. M.

Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans

Department of Physiology, The University of Texas Health Science Center, San Antonio, Texas

Submitted 14 March 2007 ; accepted in final form 24 April 2007

	ABSTRACT

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Local cooling (LC) causes a cutaneous vasoconstriction (VC). In this study, we tested whether there is a mechanism that links LC to VC nerve function via sensory nerves. Six subjects participated. Local skin and body temperatures were controlled with Peltier probe holders and water-perfused suits, respectively. Skin blood flow at four forearm sites was monitored by laser-Doppler flowmetry with the following treatments: untreated control, pretreatment with local anesthesia (LA) blocking sensory nerve function, pretreatment with bretylium tosylate (BT) blocking VC nerve function, and pretreatment with both LA and BT. Local skin temperature was slowly reduced from 34 to 29°C at all four sites. Both sites treated with LA produced an increase in cutaneous vascular conductance (CVC) early in the LC process (64 ± 55%, LA only; 42 ± 14% LA plus BT; P < 0.05), which was absent at the control and BT-only sites (5 ± 8 and 6 ± 8%, respectively; P > 0.05). As cooling continued, there were significant reductions in CVC at all sites (P < 0.05). At control and LA-only sites, CVC decreased by 39 ± 4 and 46 ± 8% of the original baseline values, which were significantly (P < 0.05) more than the reductions in CVC at the sites treated with BT and BT plus LA (–26 ± 8 and –22 ± 6%). Because LA affected only the short-term response to LC, either alone or in the presence of BT, we conclude that sensory nerves are involved early in the VC response to LC, but not for either adrenergic or nonadrenergic VC with longer term LC.

cutaneous circulation; adrenergic; bretylium; local anesthesia

Local skin cooling causes an immediate vasoconstriction, followed by a further fall in skin blood flow as cooling continues. In the presence of sensory nerve blockade or vasoconstrictor system inhibition (either presynaptically with bretylium tosylate or postsynaptically with yohimbine and propranolol), local cooling evokes an initial transitory vasodilation during the first 5 min (10, 15, 19, 21). This vasodilation is best seen under those conditions and can be minimized by reducing the rate at which cooling is performed, showing an influence of the rate of cooling on the phenomena (21).

In the longer term following this transient vasodilation, there is a net vasoconstriction, which is dependent in part on sympathetic vasoconstrictor function (5, 7, 10, 15, 21) and in part on the nitric oxide system (7, 21). Local cooling influences not only the nitric oxide synthase enzymes but also processes downstream of these enzymes in the nitric oxide vasodilator pathway (7, 21). The dependence of cooling-induced vasoconstriction on adrenergic function could be via translocation of _2C-adrenergic receptors to the vascular smooth muscle membrane due to Rho-kinase (1, 19) or an action of sensory nerves on sympathetic nerves (10), or some combination of these.

The observation that the transient vasodilation is unmasked by either sensory or sympathetic nerve blockade suggested the possibility that local cooling stimulates the vasoconstrictor nerves via a sensory nerve pathway that communicates directly to the sympathetic vasoconstrictor nerves (10). That earlier interpretation is not consistent, however, with in vitro findings of cooling causing reduced synthesis and release of norepinephrine (20). Therefore, the role of sensory nerves in longer term local cooling, and whether they play a role in the adrenergic contribution to the cutaneous vasoconstriction with local cooling, has not been established. Therefore, in this study, we directly tested whether intact sensory nerves are required for the adrenergically dependent component of cutaneous vasoconstriction with local cooling.

	METHODS

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Subjects. The Institutional Review Board of the University of Texas Health Science Center approved this study. Participants were informed of the methods and risks before written consent was obtained. A total of six (4 male and 2 female) subjects participated in the study. All subjects were healthy nonsmokers, taking no medications. They refrained from alcoholic and caffeinated beverages for a period of at least 12 h before the study. The menstrual status was noted for the women participants but was not considered, because previous studies have shown the vasoconstrictor response to local cooling to be unaffected by reproductive hormones (4).

Measurements. Skin blood flow was monitored by laser-Doppler flowmetry (Moor Instruments, Axminster, UK) on the ventral aspect of the forearm and expressed as laser-Doppler flow (LDF) (8). LDF measurements have been shown to be exclusive to the skin and are not affected by underlying skeletal muscle blood flow (17). The LDF probes were housed in custom-built metal Peltier cooling/heating probe holders (7, 10, 21). These devices, which allow local temperature (T_loc) of the skin surrounding the LDF measurement site to be controlled independently of whole body skin temperature (T_sk), cover 6.3 cm² with the exception of a small aperture (0.28 cm²) in the center of the holder to enable blood flow measurement. Local skin temperature was assessed by a thermocouple placed between the skin and probe holder. Mean arterial pressure (MAP) was measured continuously at the left middle finger by photoplethysmography (Finapres, Ohmeda, WI) (14). The ratio of LDF to MAP was calculated as an index of cutaneous vascular conductance (CVC). Water-perfused suits, which covered the entire body except the head, hands, feet, and the experimental forearm, were used to control T_sk. T_sk was calculated as the weighted average of temperature readings from thermocouples at the following sites: chest, upper back, lower back, abdomen, thigh, and calf (18). To minimize tonic vasoconstrictor activity, whole body T_sk values were kept at 36°C, except for a 3-min period of aggressive whole body cooling to 31°C to test for adequate blockade of vasoconstrictor nerve neurotransmitter release (11). Whole body T_sk was kept at the slightly warm temperature of 36°C because we wanted to remove as much of the tonic release of norepinephrine as possible, without increasing T_sk so much as to increase blood flow. T_loc for the 6.3-cm² area surrounding LDF sites was controlled at 34°C during the baseline period and was slowly reduced to 29°C (–0.33°C/min) during the local cooling protocol. All variables were sampled at 1-s intervals and stored as 20-s averages for off-line analysis.

Blockade of transmitter release from vasoconstrictor nerve terminals was achieved through iontophoresis of bretylium tosylate (BT; Schweizerhall, South Plainfield, NJ) at a concentration of 10 mM at 250 µA for 10 min to a 0.64-cm² area of skin (11). Sensory nerve blockade was achieved through the use of a topical local anesthetic cream (Fougera, Melville, NY) consisting of lidocaine (2.5%) and prilocaine (2.5%) (10). The cream was applied to an area of 8 cm² under an occlusive dressing, where it was left for a minimum of 2 h. The area was tested for sensory loss both before the study began and at its completion.

Protocol. The protocol was performed to test whether functional sensory nerves are required for the adrenergic portion of the vasoconstrictor response to local cooling. Four sites were randomly selected on the ventral aspect of the forearm. The treatment of those sites and the protocol are outlined in Fig. 1. Site 1 was an untreated control; site 2 was treated with BT to inhibit the release of norepinephrine from vasoconstrictor nerves; site 3 was treated with topical local anesthetic to inhibit sensory nerve function; and, finally, site 4 was treated with the combination of BT and local anesthetic to inhibit both systems. We reasoned that if a significant portion of the vasoconstriction to local cooling was due to sensory nerve stimulation of vasoconstrictor nerves, then the degree of vasoconstriction at sites without functional adrenergic nerves, without functional sensory nerves, or lacking both would be approximately equal and all would have responses reduced from those seen at control sites. After a minimum of 2 h had elapsed, allowing maximum anesthetization, those sites (sites 3 and 4, Fig. 1) were tested by pin prick to confirm that they were anesthetized. Subjects were then instrumented as described above. After the subject had been lying quietly for a minimum of 30 min, baseline measurements were recorded for 10 min. After a 3-min period of whole body cooling to test for the adequacy of vasoconstrictor nerve blockade by BT (sites 2 and 4, Fig. 1), T_sk was returned to 36°C. This also verified whether vasoconstrictor nerve function remained intact in the presence of local anesthesia. T_loc at all sites was maintained at 34°C throughout this portion of the study. Next, T_loc was reduced to 29°C, at a rate of –0.33°C/min, for the next 15 min. This slow rate was used to lessen the early transitory vasodilation (21). Once CVC had stabilized (20 min), T_loc was returned to 34°C. Whole body T_sk was again cooled to 31°C to confirm inhibition of vasoconstrictor nerve activity with BT treatment. A reduction in CVC of >10% at BT-treated sites was taken to indicate inadequate blockade, and data from such sites were excluded from further analysis (11). Finally, sites treated with local anesthesia were tested, by pin prick, to ensure they were still anesthetized. No sites had to be excluded on these bases in this study.

View larger version (11K): [in this window] [in a new window]   Fig. 1. Protocol used to verify whether sensory nerves were involved in the vasoconstrictor response to local cooling at 4 sites: 1, untreated control; 2, treated with bretylium (BT); 3, treated with local anesthesia (LA); and 4, treated with both BT and LA. After 10 min of baseline measures, local cooling commenced at a rate of –0.33°C/min, reducing local temperature (Tloc) from 34 to 29°C over a 15-min period. Once local temperature of 29°C was reached, it was maintained at this level for a further 15 min to allow stabilization of cutaneous vascular conductance (CVC). Warming was performed slowly (1°C/min) back to 34°C and held at this temperature for 10 min. Following this, aggressive whole body cooling (WBC) from 34 to 31°C was performed for 3 min to confirm adequate vasoconstrictor nerve blockade with BT. LC, local cooling; Tskin, whole body skin temperature.

	RESULTS

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Figure 2 displays representative responses to the protocol from all four sites. Note the pronounced vasodilation early during the local cooling at both sites with local anesthetic treatment (sites 3 and 4). Importantly, after 25 min of local cooling, the site with only local anesthetic (site 3) displayed a similar degree of vasoconstriction as shown by the control site (site 1). The site treated with both local anesthesia and BT had a reduction in CVC similar to that at the BT-only sites. Those two sites failed to achieve the same degree of vasoconstriction as the other two sites. Because of this biphasic response at sites treated with local anesthesia, results are compared for the first 5 min and the final 5 min of local cooling.

View larger version (11K): [in this window] [in a new window]   Fig. 2. Representative responses from 1 subject to the protocol outlined in Fig. 1. Note the pronounced transitory vasodilation at sites 3 and 4, both of which were treated with LA. This was despite the slower local cooling protocol, which showed virtually no response during this time period at the BT-treated sites. Importantly, there were larger and similar degrees of vasoconstriction at the control and the LA-only sites (sites 1 and 3) compared with the BT-treated sites (sites 2 and 4) at the end of cooling. This suggests no linkage between sensory nerves and vasoconstrictor nerves.

View larger version (6K): [in this window] [in a new window]   Fig. 3. Early local cooling: average responses in CVC, as percent changes, to local cooling at all 4 sites during the first 5–10 min of local cooling. There was a pronounced early vasodilation at the 2 sites treated with LA but no significant change at control and BT-treated sites (n = 6). *P < 0.05, different from control and BT-treated sites.

View larger version (5K): [in this window] [in a new window]   Fig. 4. Late local cooling: average responses in CVC, as percent changes, to the last 15 min of local cooling at all 4 sites. Importantly, observe the similar large reductions in CVC at the control and LA-treated sites. Furthermore, note the similar decreases at the BT and BT+LA sites, additionally suggesting no role for sensory nerves during the late local cooling vasoconstrictor response (n = 6). *P < 0.05, different from precooling. P < 0.05, different from control and LA-treated sites.

	DISCUSSION

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The notion that sensory nerves might be involved in the cutaneous vasoconstrictor response to local cooling initially derived from responses to local cooling during the early vasodilation phase, which is seen if sensory nerves are blocked or, to a lesser extent, if vasoconstrictor nerve neurotransmission is blocked (10, 15, 21). This correspondence suggested the potential for a series linkage. The current data, however, do not support such a link between sensory nerves and vasoconstrictor nerves during the longer term cutaneous vasoconstrictor response to local cooling, because that similarity in pattern no longer continues when the local cooling is performed slowly. This proposition is also based on the findings of a similar longer term vasoconstrictor response to local cooling at the untreated control sites and at those sites treated with local anesthesia. There also appears to be no sensory nerve involvement in the nonadrenergic later phase vasoconstriction to local cooling. This conclusion is supported by results from the BT sites and local anesthesia plus BT sites having similar degrees of vasoconstriction. At BT-treated sites, only the nonadrenergic component of the local cooling response is functional (7, 21). If that portion were dependent on sensory nerve activation, one would expect a smaller vasoconstriction at sites treated with local anesthesia.

Lindblad et al. (12) also examined the influence of the infiltration of local anesthetic in the response in finger blood flow to brief (30 s) local cooling. They found such treatments block completely the vasoconstrictor response. The short duration and rapidity of the cooling in that study precluded comparison with the current study, however. Furthermore, it is not known whether dorsal finger skin and forearm skin have the same mechanisms for locally induced vasoconstrictor responses. For example, the authors did not report a vasodilator response to rapid local cooling in locally anesthetized skin, as was seen in forearm skin in the current study and earlier (10).

The rate of cooling has other important roles, as well. For example, the vasoconstriction seen early in local cooling in previous studies (10, 21) was not seen until later in the procedure in the current study, but the degree and rate of cooling were less. Also, the initial vasodilation seen at sites pretreated with BT is rate dependent, requiring rapid cooling for the vasodilator phase to be pronounced (21). It is also important to note that in the earlier study (10), an initial vasodilation was noted if either sensory or sympathetic function was inhibited; that study involved relatively rapid cooling. With slow local cooling, a clear difference was revealed in which sites treated with local anesthesia showed a vasodilation, but sites treated with BT only did not. This observation supports our conclusion of a separation between sensory and sympathetic contributions to the responses to local cooling. Furthermore, if repeated bouts of local cooling are applied, the initial vasodilation, at least at the BT-treated sites, decreases in magnitude (21). This, plus the transient nature of the response and its rate dependency, suggests that the vasodilator phenomenon might be mediated through a depletable intermediate. Regardless of this speculation, ascertaining the basis of this response remains problematic, and its origin remains a mystery.

The vasoconstriction elicited from adrenergic-dependent mechanisms would appear most likely to be due to cooling causing a translocation of _2C-receptors from the Golgi apparatus to the vascular smooth muscle cell surface by Rho-kinase (1, 2, 19). This effect on adrenergic receptors occurs despite reduced synthesis of norepinephrine from sympathetic nerve endings and a general inhibition of the contractile process (3, 6, 20). As such, the vasoconstriction that occurs in response to the lower local temperatures might be mediated entirely by Rho-kinase through the translocation of _2C-receptors. If, indeed, local cooling decreases synthesis and release of norepinephrine in vivo as it does in vitro, then the adrenergic-dependent portion of the vasoconstriction to local cooling would be entirely due to an increased number of _2C-receptors. In that case, one might speculate that the increased number of _2C-receptors more than balances any reductions in transmitter synthesis and release and, furthermore, that tonic transmitter release is necessary to stimulate those receptors. This is, however, speculation and requires further investigation.

Figure 5 shows our current working model of how local cooling exerts its effects on the cutaneous circulation. It is based on this and previous studies from our laboratory and those of others. Early in the local cooling process (Fig. 5A), sensory and sympathetic nerves are stimulated to cause a vasoconstriction. This is reversed if either of these systems is inhibited, unmasking a transitory vasodilation. Later in the local cooling process (Fig. 5B), nitric oxide synthase activity is reduced, as is the release of transmitter from sympathetic nerves; there is also a translocation of _2C-receptors to the cell surface. The reduction in nitric oxide activity and the translocation of _2C-receptors appears to be mediated by Rho- kinase (1, 19).

View larger version (8K): [in this window] [in a new window]   Fig. 5. Model of the mechanisms contributing to the cutaneous vascular responses to local cooling. Local cooling has an inhibitory effect on sympathetic nerve function and the nitric oxide pathway, affecting both the nitric oxide synthase enzyme activity and the utilization of nitric oxide. Local cooling also has an excitatory role in stimulating Rho-kinase (ROCK), eliciting the translocation of 2C-receptors. Under conditions of sensory nerve blockade, sympathetic nerve inhibition and/or - and -receptor antagonism, a transitory dilation is apparent early in the cooling process, which is succeeded by a later nonneural vasoconstriction. The mechanism for the early vasodilation is unknown, yet it is apparent that sensory nerves play a key role. The later nonneural vasoconstriction is via the nitric oxide vasodilator pathway and the translocation of 2C-receptors, both of which are heavily dependent on ROCK activation. Not shown are the effects of local cooling on noradrenaline release and synthesis, or vascular smooth muscle function. +, Excitatory stimuli; –, inhibitory stimuli.

The specificity of the local anesthesia acting only on the sensory nerves and not affecting the vasoconstrictor nerves was again confirmed (10). Intuitively, it would be expected that the combination of lidocaine and prilocaine would interfere with nerve conduction of all small myelinated and unmyelinated fibers; nevertheless, that does not appear to be the case. This might be due to sensory nerves being more superficial than the vasoconstrictor nerves. The topical application of anesthesia would require a greater distance for the diffusion of these substances to the vasoconstrictor nerves.

In summary, we have confirmed that the longer term vasoconstrictor response to local cooling can be completely achieved without functional sensory nerves. Interestingly, although intact sensory nerves are not required for a complete vasoconstrictor response to local cooling in the cutaneous circulation, sensory nerve function is required for vasoconstriction to occur early in the local cooling process. Without functional sensory nerves, a transient vasodilation is unmasked even during slow local cooling. However, the current study shows clearly that the involvement of sensory nerves does not induce an axon-reflex stimulation of release of norepinephrine from sympathetic nerves. On the basis of work by others, the adrenergic portion of the response to local cooling would appear to involve largely a postsynaptic translocation of _2C-receptors mediated by Rho-kinase (1, 19). It would be most likely that the effects of local cooling via translocation of _2C-receptors would also be dependent on the tonic release of norepinephrine. In the present study, that should have been low, because whole body T_sk was kept at a slightly warm (36°C) temperature throughout. We do not know, however, if all norepinephrine release had been eliminated.

	GRANTS

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This study was supported by National Heart, Lung, and Blood Institute Grant R01 HL-059166.

	ACKNOWLEDGMENTS

 
We thank the volunteers for their participation.

	FOOTNOTES

 

Address for reprint requests and other correspondence: J. M. Johnson, Dept. of Physiology-MSC 7756, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 (e-mail: johnson{at}uthscsa.edu)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

	REFERENCES

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1. Bailey SR, Eid AH, Mitra S, Flavahan S, Flavahan NA. Rho kinase mediates cold-induced constriction of cutaneous arteries: role of 2C-adrenoceptor translocation. Circ Res 94: 1367–1374, 2004.[Abstract/Free Full Text]
2. Bailey SR, Mitra S, Flavahan S, Flavahan NA. Reactive oxygen species from smooth muscle mitochondria initiate cold-induced constriction of cutaneous arteries. Am J Physiol Heart Circ Physiol 289: H243–H250, 2005.[Abstract/Free Full Text]
3. Boles PJ, Verbeuren TJ, Vanhoutte PM. Moderate cooling depresses the accumulation of newly synthesized catecholamines in isolated canine saphenous veins. Experientia 41: 1374–1377, 1985.[CrossRef][Web of Science][Medline]
4. Charkoudian N, Stephens DP, Pirkle KC, Kosiba WA, Johnson JM. Influence of female reproductive hormones on local thermal control of skin blood flow. J Appl Physiol 87: 1719–1723, 1999.[Abstract/Free Full Text]
5. Ekenvall L, Lindblad LE, Norbeck O, Etzell BM. -Adrenoceptors and cold-induced vasoconstriction in human finger skin. Am J Physiol Heart Circ Physiol 255: H1000–H1003, 1988.[Abstract/Free Full Text]
6. Flavahan NA, Vanhoutte PM. Effect of cooling on -1 and -2 adrenergic responses in canine saphenous and femoral veins. J Pharmacol Exp Ther 238: 139–147, 1986.[Abstract/Free Full Text]
7. Hodges GJ, Zhao K, Kosiba WA, Johnson JM. The involvement of nitric oxide in the cutaneous vasoconstrictor response to local cooling in humans. J Physiol 574: 849–857, 2006.[Abstract/Free Full Text]
8. Johnson JM. The cutaneous circulation. In: Laser-Doppler Blood Flowmetry, edited by Shepherd AP and Öberg PA. New York: Springer, 2004, p. 121–139.
9. Johnson JM, Proppe DW. Cardiovascular adjustments to heat stress. In: Handbook of Physiology. Environmental Physiology. Bethesda MD: Am Physiol Soc, 1996, sect. 4, vol. 1, p. 215–243.
10. Johnson JM, Yen TC, Zhao K, Kosiba WA. Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling. Am J Physiol Heart Circ Physiol 288: H1573–H1579, 2005.[Abstract/Free Full Text]
11. Kellogg DL Jr, Johnson JM, Kosiba WA. Selective abolition of adrenergic vasoconstrictor responses in skin by local iontophoresis of bretylium. Am J Physiol Heart Circ Physiol 257: H1599–H1606, 1989.[Abstract/Free Full Text]
12. Lindblad LE, Ekenvall L, Klingstedt C. Neural regulation of vascular tone and cold induced vasoconstriction in human finger skin. J Auton Nerv Syst 30: 169–173, 1990.[CrossRef][Web of Science][Medline]
13. Öberg PA. Laser-Doppler flowmetry. Crit Rev Biomed Eng 18: 125–163, 1990.[Web of Science][Medline]
14. Parati G, Casadei R, Groppelli A, Di Rienzo M, Mancia G. Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing. Hypertension 13: 647–655, 1989.[Abstract/Free Full Text]
15. Pérgola PE, Kellogg DL Jr, Johnson JM, Kosiba WA, Solomon DE. Role of sympathetic nerves in the vascular effects of local temperature in human forearm skin. Am J Physiol Heart Circ Physiol 265: H785–H792, 1993.[Abstract/Free Full Text]
16. Rowell LB. Cardiovascular aspects of human thermoregulation. Circ Res 52: 367–379, 1983.[Web of Science][Medline]
17. Saumet JL, Kellogg DL Jr, Taylor WF, Johnson JM. Cutaneous laser-Doppler flowmetry: influence of underlying muscle blood flow. J Appl Physiol 65: 478–481, 1988.[Abstract/Free Full Text]
18. Taylor WF, Johnson JM, Kosiba WA, Kwan CM. Cutaneous vascular responses to isometric handgrip exercise. J Appl Physiol 66: 1586–1592, 1989.[Abstract/Free Full Text]
19. Thompson-Torgerson CS, Holowatz LA, Flavahan NA, Kenney WL. Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin. Am J Physiol Heart Circ Physiol 292: H1700–H1705, 2007.[Abstract/Free Full Text]
20. Vanhoutte PM. Physical factors of regulation. In: Handbook of Physiology. The Cardiovascular System. Bethesda, MD: Am Physiol Soc, 1980, sect. 2, vol. II, chapt. 16, p. 443–474.
21. Yamazaki F, Sone R, Zhao K, Alvarez GE, Kosiba & Johnson JM WA. Rate dependency and role of nitric oxide in the vascular response to direct cooling in human skin. J Appl Physiol 100: 42–50, 2006.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) All Versions of this Article: 293/1/H784    most recent 00323.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Hodges, G. J. Articles by Johnson, J. M. Search for Related Content PubMed PubMed Citation Articles by Hodges, G. J. Articles by Johnson, J. M.