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Article: ATP as a peripheral mediator of pain.

Hamilton, S G / McMahon, S B

2000 Volume 81, Issue 1-3, Page(s) 187–194

Abstract: This article reviews the extent to which recent studies substantiate the hypothesis that ATP functions as a peripheral pain mediator. The discovery of the P2X family of ion channels (for which ATP is a ligand) and, in particular, the highly selective ... ...

Abstract	This article reviews the extent to which recent studies substantiate the hypothesis that ATP functions as a peripheral pain mediator. The discovery of the P2X family of ion channels (for which ATP is a ligand) and, in particular, the highly selective distribution of the P2X(3) receptor within the rat nociceptive system has inspired a variety of approaches to elucidate the potential role of ATP as a pain mediator. ATP elicits excitatory inward currents in small diameter sensory ganglion cells. These currents resemble those elicited by ATP on recombinantly expressed heteromeric P2X(2/3) channels as well as homomultimers consisting of P2X(2) and P2X(3). In vivo behavioural models have characterised the algogenic properties of ATP in normal conditions and in models of peripheral sensitisation. In humans, iontophoresis of ATP induces modest pain. In rats and humans the response is dependent on capsaicin sensitive neurons and is augmented in the presence of inflammatory mediators. Since ATP can be released in the vicinity of peripheral nociceptive terminals under a variety of conditions, there exists a purinergic chain of biological processes linking tissue damage to pain perception. The challenge remains to prove a physiological role for endogenous ATP in activating this chain of events.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Adenosine Triphosphate/physiology ; Animals ; Humans ; Nociceptors/physiology ; Pain/physiopathology ; Rats ; Receptors, Purinergic/physiology ; Signal Transduction/physiology
Chemical Substances	Receptors, Purinergic ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2000-07-03
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	446196-4
ISSN	1872-7476 ; 0165-1838
ISSN (online)	1872-7476
ISSN	0165-1838
DOI	10.1016/s0165-1838(00)00137-5
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Article: The effects of inflammation and inflammatory mediators on nociceptive behaviour induced by ATP analogues in the rat.

Hamilton, S G / Wade, A / McMahon, S B

British journal of pharmacology

1999 Volume 126, Issue 1, Page(s) 326–332

Abstract: 1. We have studied the behavioural effects of intraplantar injections of adenosine 5'-triphosphate (ATP) and related compounds in freely moving rats and investigated whether these nociceptive effects are augmented in the presence of inflammatory ... ...

Abstract	1. We have studied the behavioural effects of intraplantar injections of adenosine 5'-triphosphate (ATP) and related compounds in freely moving rats and investigated whether these nociceptive effects are augmented in the presence of inflammatory mediators. 2. We find that in normal animals ATP and analogues produce dose-dependent nocifensive behaviour (seen as bursts of elevation of the treated hindpaw), and localized thermal hyperalgesia. The rank order of potency was: alpha,beta-methyleneadenosine 5'-triphosphate (alpha,beta-methylene ATP) > 2-methylthioadenosine triphosphate (2-methylthio ATP) > ATP. After neonatal treatment with capsaicin, to destroy small calibre primary sensory neurones, nocifensive behaviour was largely absent. 3. The effects of ATP analogues were assessed in three models of peripheral sensitization: 2 h after dilute intraplantar carrageenan (0.25% w v(-1)); 24 h after irradiation of the hindpaw with ultraviolet (U.V.) B; immediately following prostaglandin E2 (PGE2) treatment. In all models the effect of alpha,beta-methylene ATP was greatly augmented. After carrageenan, significant hindpaw-lifting behaviour activity was induced by injection of only 0.05 nmol of alpha,beta-methylene ATP, some 100 times less than necessary in normal skin. 4. Our data suggest that it is much more likely that endogenous levels of ATP will reach levels capable of exciting nociceptors in inflamed versus normal skin. Our data also suggest the involvement of P2X3 receptor subunits in ATP-induced nociception.
MeSH term(s)	Adenosine Triphosphate/analogs & derivatives ; Adenosine Triphosphate/pharmacology ; Animals ; Animals, Newborn ; Capsaicin/pharmacology ; Carrageenan/pharmacology ; Dinoprostone/pharmacology ; Dose-Response Relationship, Drug ; Excipients/pharmacology ; Hindlimb/drug effects ; Hindlimb/pathology ; Hyperalgesia/chemically induced ; Inflammation/chemically induced ; Inflammation/physiopathology ; Inflammation Mediators/pharmacology ; Inflammation Mediators/therapeutic use ; Male ; Nociceptors/drug effects ; Nociceptors/radiation effects ; Oxytocics/pharmacology ; Pain/chemically induced ; Pain/physiopathology ; Pain/prevention & control ; Pain Threshold/drug effects ; Rats ; Rats, Wistar ; Thionucleotides/pharmacology ; Ultraviolet Rays
Chemical Substances	Excipients ; Inflammation Mediators ; Oxytocics ; Thionucleotides ; Adenosine Triphosphate (8L70Q75FXE) ; Carrageenan (9000-07-1) ; Dinoprostone (K7Q1JQR04M) ; alpha,beta-methyleneadenosine 5'-triphosphate (NYX13NT29D) ; Capsaicin (S07O44R1ZM) ; 2-methylthio-ATP (Y37441OBL1)
Language	English
Publishing date	1999-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1038/sj.bjp.0702258
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Article: Blood loss in pelvic fractures.

Hamilton, S G

Proceedings of the Royal Society of Medicine

1973 Volume 66, Issue 7, Page(s) 629–631

MeSH term(s)	Accidents, Occupational ; Accidents, Traffic ; Adult ; Blood Transfusion ; Collateral Circulation ; Fractures, Bone/complications ; Fractures, Bone/therapy ; Hematoma/diagnostic imaging ; Hematoma/surgery ; Hemorrhage/etiology ; Hemorrhage/therapy ; Humans ; Iliac Artery/injuries ; Iliac Artery/surgery ; Ligation ; Male ; Pelvic Bones/injuries ; Radiography ; Retroperitoneal Space
Language	English
Publishing date	1973-07
Publishing country	England
Document type	Journal Article
ZDB-ID	209243-8
ISSN	0035-9157
ISSN	0035-9157
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Article: Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin.

Hamilton, S G / McMahon, S B / Lewin, G R

The Journal of physiology

2001 Volume 534, Issue Pt. 2, Page(s) 437–445

Abstract: 1. ATP can elicit pain in humans and, together with other P2X channel agonists, can produce nocifensive responses in rodents. We used the rat in vitro skin-nerve preparation to quantify primary afferent responses to ATP and its stable analogue alpha,beta- ...

Abstract	1. ATP can elicit pain in humans and, together with other P2X channel agonists, can produce nocifensive responses in rodents. We used the rat in vitro skin-nerve preparation to quantify primary afferent responses to ATP and its stable analogue alpha,beta-methylene ATP in normal and carrageenan-inflamed skin. 2. Both ATP and alpha,beta-methylene ATP were found to specifically activate the peripheral terminals of Adelta and C-fibre nociceptors in the skin. Thirty-nine per cent of the nociceptors tested responded to the maximal dose of alpha,beta-methylene ATP (5 mM). In contrast, non-nociceptive, low-threshold mechano-sensitive fibres were never activated by the same agonist concentrations. 3. Amongst the nociceptor population, C-mechanoheat fibres (C-MH or polymodal nociceptors) were markedly more responsive to P2X agonists than mechanonociceptors (C-M nociceptors) with Adelta- or C-fibre axons. Both C-mechanoheat and C-mechanonociceptors were activated by alpha,beta-methylene ATP doses as low as 50 microM. 4. In skin inflamed with carrageenan 3-4 h before recording both the number of responsive C-fibre nociceptors and their response magnitude increased. The increased neural response under inflammatory conditions was largely observed in C-mechanoheat or polymodal nociceptors. After low doses of P2X agonists C-MH fibres but not C-M fibres developed elevated ongoing activity and this effect was only seen after carrageenan inflammation. The time course of alpha,beta-methylene ATP-evoked discharges in nociceptors was found to correlate well with the time course of behavioural nocifensive responses in rats to the same agonist described in a previous study (Hamilton et al. 1999). 5. We conclude that the rapid increase in the number of alpha,beta-methylene ATP responsive nociceptors and the increased magnitude of the neural response following carrageenan inflammation explains why very low concentrations of such agonists can cause pain in inflammatory states.
MeSH term(s)	Adenosine Triphosphate/analogs & derivatives ; Adenosine Triphosphate/pharmacology ; Animals ; Carrageenan ; Dermatitis/physiopathology ; Dose-Response Relationship, Drug ; Female ; In Vitro Techniques ; Male ; Nociceptors/drug effects ; Nociceptors/physiology ; Pain/physiopathology ; Purinergic P2 Receptor Agonists ; Rats ; Rats, Wistar ; Receptors, Purinergic P2/physiology ; Skin/innervation ; Skin/physiopathology
Chemical Substances	Purinergic P2 Receptor Agonists ; Receptors, Purinergic P2 ; Adenosine Triphosphate (8L70Q75FXE) ; Carrageenan (9000-07-1) ; alpha,beta-methyleneadenosine 5'-triphosphate (NYX13NT29D)
Language	English
Publishing date	2001-07-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1111/j.1469-7793.2001.00437.x
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Article: Anesthesia by acupuncture.

Hamilton, S G

British medical journal

1972 Volume 4, Issue 5834, Page(s) 232–233

MeSH term(s)	Acupuncture Therapy ; Anesthesia ; Breathing Exercises ; China ; Female ; Gastrectomy ; Humans ; Lung/surgery
Language	English
Publishing date	1972-10-28
Publishing country	England
Document type	Journal Article
ZDB-ID	80088-0
ISSN	0007-1447 ; 0267-0623 ; 0959-8138 ; 0959-8146
ISSN	0007-1447 ; 0267-0623 ; 0959-8138 ; 0959-8146
DOI	10.1136/bmj.4.5834.232-b
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Article: Congenital pocomelia in monozygotic twins.

Hamilton, S G

British medical journal

1967 Volume 4, Issue 5578, Page(s) 524–526

MeSH term(s)	Arm/embryology ; Diseases in Twins ; Ectromelia/diagnostic imaging ; Humans ; Leg/embryology ; Male ; Radiography
Language	English
Publishing date	1967-12-02
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	80088-0
ISSN	0007-1447 ; 0267-0623 ; 0959-8138 ; 0959-8146
ISSN	0007-1447 ; 0267-0623 ; 0959-8138 ; 0959-8146
DOI	10.1136/bmj.4.5578.524
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Article: Spontaneous rupture of the oesophgus.

Hamilton, S G

The British journal of surgery

1967 Volume 54, Issue 4, Page(s) 304–306

MeSH term(s)	Bronchoscopy ; Coronary Disease/diagnosis ; Diagnosis, Differential ; Emphysema/etiology ; Esophageal Perforation/diagnosis ; Esophageal Perforation/therapy ; Female ; Humans ; Male ; Mediastinal Emphysema/diagnostic imaging ; Middle Aged ; Pleural Effusion/etiology ; Radiography ; Rupture, Spontaneous/diagnosis ; Vomiting/etiology
Language	English
Publishing date	1967-04
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2985-3
ISSN	0007-1323 ; 0263-1202 ; 1355-7688
ISSN	0007-1323 ; 0263-1202 ; 1355-7688
DOI	10.1002/bjs.1800540413
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Article: Surgical anatomy of donor sites for free muscle transplantation to the paralyzed face.

Hamilton, S G / Terzis, J K

Clinics in plastic surgery

1984 Volume 11, Issue 1, Page(s) 197–201

MeSH term(s)	Facial Muscles/innervation ; Facial Paralysis/surgery ; Humans ; Muscles/anatomy & histology ; Muscles/transplantation
Language	English
Publishing date	1984-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	193117-9
ISSN	1558-0504 ; 0094-1298
ISSN (online)	1558-0504
ISSN	0094-1298
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Article: The scapular free flap.

Hamilton, S G / Morrison, W A

British journal of plastic surgery

1982 Volume 35, Issue 1, Page(s) 2–7

Abstract: A purely cutaneous free flap overlying the infraspinous region of the scapula has been used successfully in three cases. It is of intermediate thickness, predominantly hairless and is based on the cutaneous branch of the circumflex scapular artery. Te ... ...

Abstract	A purely cutaneous free flap overlying the infraspinous region of the scapula has been used successfully in three cases. It is of intermediate thickness, predominantly hairless and is based on the cutaneous branch of the circumflex scapular artery. Te dissection of the flap is easy, quick and safe, resulting in a minimal pedicle length of 3 cm but this can be lengthened significantly by the inclusion of the more proximal vessels. The vessel diameter and its distribution make revascularization predictable. In this vessels. The vessel diameter and its distribution make revascularization predictable. In this series, the longest flap used was 24 cm and the widest was 12 cm, the width being limited by the ability to achieve primary closure. The only donor site disability is related to a tight linear transverse scar. These is no functional limitation nor distortion of the axillary contours. This contrasts with the thicker and widely used latissimus dorsi free flap. The scapular flap should replace the latissimus dorsi flap where the size of the defect to be covered is within the critical dimensions of this flap. The scapular flap can be combined with the latissimus dorsi flap for larger areas of skin cover, or the two flaps can be separated still based on their common vascular pedicle to cover two areas with diverging axes.
MeSH term(s)	Adult ; Elbow Joint/injuries ; Foot Diseases/surgery ; Humans ; Leg Injuries/surgery ; Male ; Methods ; Middle Aged ; Shoulder ; Skin Ulcer/surgery ; Surgical Flaps
Language	English
Publishing date	1982-01
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	218112-5
ISSN	0007-1226
ISSN	0007-1226
DOI	10.1016/0007-1226(82)90075-3
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Article: ATP in human skin elicits a dose-related pain response which is potentiated under conditions of hyperalgesia.

Hamilton, S G / Warburton, J / Bhattacharjee, A / Ward, J / McMahon, S B

Brain : a journal of neurology

2000 Volume 123 Pt 6, Page(s) 1238–1246

Abstract: Despite the considerable interest in the possibility that ATP may function as a peripheral pain mediator, there has been little quantitative study of the pain-producing effects of ATP in humans. Here we have used iontophoresis to deliver ATP to the ... ...

Abstract	Despite the considerable interest in the possibility that ATP may function as a peripheral pain mediator, there has been little quantitative study of the pain-producing effects of ATP in humans. Here we have used iontophoresis to deliver ATP to the forearm skin of volunteers who rated the magnitude of the evoked pain on a visual analogue scale. ATP consistently produced a modest burning pain, which began within 20 s of starting iontophoresis and was maintained for several minutes. Persistent iontophoresis of ATP led to desensitization within 12 min but recovery from this was almost complete 1 h later. Different doses of ATP were delivered using different iontophoretic driving currents. Iontophoresis of ATP produced a higher pain rating than saline, indicating that the pain was specifically caused by ATP. The average pain rating for ATP, but not saline, increased with increasing current. Using an 0.8 mA current, subjects reported pain averaging 27.7 +/- 2.8 (maximum possible = 100). Iontophoresis of ATP caused an increase in blood flow, as assessed using a laser Doppler flow meter. The increase in blood flow was significantly greater using ATP than saline in both the iontophoresed skin (P < 0.01) and in the surrounding skin, 3 mm outside the iontophoresed area (P < 0.05). The pain produced by ATP was dependent on capsaicin-sensitive sensory neurons, since in skin treated repeatedly with topical capsaicin pain was reduced to less than 25% of that elicited on normal skin (2.1 +/- 0.4 compared with 9.3 +/- 1.5 on normal skin). Conversely, the pain-producing effects of ATP were greatly potentiated in several models of hyperalgesia. Thus, with acute capsaicin treatment when subjects exhibited touch-evoked hyperalgesia but no ongoing pain, there was a threefold increase in the average pain rating during ATP iontophoresis (22.7 +/- 3.1) compared with pre-capsaicin treatment (7.8 +/- 2.6). Moreover, ATP iontophoresed into skin 24 h after solar simulated radiation (2 x minimal erythymic dose) resulted in double the pain rating of normal skin, increasing from 15.3 +/- 4.1 to 32.7 +/- 4.1. The pain response to saline was not significantly altered after UV irradiation at any time-point studied. We conclude that ATP produces pain by activating capsaicin-sensitive nociceptive afferents when applied to skin. The possibility that ATP activates nociceptors indirectly via its degradation products cannot be ruled out. The effects of ATP are dose-dependent and responses desensitize only slowly. In inflammatory conditions, ATP may be a potent activator of nociceptors and an endogenous mediator of pain.
MeSH term(s)	Adenosine Triphosphate/administration & dosage ; Adenosine Triphosphate/adverse effects ; Adult ; Capsaicin/administration & dosage ; Capsaicin/adverse effects ; Drug Synergism ; Female ; Humans ; Hyperalgesia/chemically induced ; Hyperalgesia/physiopathology ; Iontophoresis ; Male ; Neurons, Afferent/drug effects ; Neurons, Afferent/physiology ; Nociceptors/drug effects ; Nociceptors/physiology ; Pain/chemically induced ; Pain/physiopathology ; Regional Blood Flow ; Skin/blood supply ; Skin/innervation ; Skin/radiation effects ; Touch/drug effects ; Ultraviolet Rays
Chemical Substances	Adenosine Triphosphate (8L70Q75FXE) ; Capsaicin (S07O44R1ZM)
Language	English
Publishing date	2000-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	0006-8950
ISSN	0006-8950
DOI	10.1093/brain/123.6.1238
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