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R D Helme

Publications and source records attributed to R D Helme.

At least 73 records · Page 4Linked to original sources
PubMed1989

Can psychometric tools be used to analyse pain in a geriatric population?

Pain is both a sensory and an emotional experience. In a multidisciplinary pain management clinic for a geriatric population, pain and mood have been assessed prior to the initiation of management in 49 of 100 referred patients. Patients have been assessed clinically, for psychological disability using the profile of mood states (POMS) and a visual analogue scale for mood, for pain using the McGill pain questionnaire (short form), word descriptor scale and visual analogue scale and for activities of daily living (ADL) using the Disability and Impairment Interview Schedule and the Rapid Disability Rating Scale -2. All testing has followed initial screening to exclude dementia. For the group assessed by psychometric measures, median age was 75 years (range 56 to 91); 41 were female. Major pathologies were degenerative musculoskeletal disease (15), post-herpetic neuralgia (9), and psychiatric conditions (7). Intra-test item correlations were found to be significant for the McGill questionnaire and the POMS. Inter-test correlations were observed for pain measures (McGill present pain intensity with VAS pain, r = 0.67; with word descriptor, 0.64; p less than 0.001), for ADL measures (r = 0.53, p less than 0.001) and for measures of mood (VAS mood with POMS (depression), r = 0.45; p less than 0.001; with POMS (anxiety), r = 0.35; p less than 0.01. There was no significant correlation between measures of mood and pain on the McGill scale. The data to this time support the view that standard psychometric tools can be used reliably to evaluate pain, mood and activity in this population. Furthermore, it appears that mood and pain may be measured separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

VIP modulates substance P-induced plasma extravasation in vivo.

Substance P (SP), a putative mediator of neurogenic inflammation, has previously been shown to induce plasma extravasation when exogenously perfused over a blister base induced on the rat hind foot pad. Using the same animal model, we have studied the role of vasoactive intestinal polypeptide (VIP), one of the neuromodulators in primary afferent neurons, on SP-induced plasma extravasation. At all concentrations tested (2.5, 5 and 10 microM), VIP did not cause plasma extravasation by itself, however, it increased that due to 1 microM SP, in a dose-related manner. We have also studied the effect of VIP on the local blood flow in the blister base using a laser doppler-flowmeter. VIP was also found to increase the local blood flow in a dose-dependent manner. The present results provide evidence for the first time in vivo of a role for VIP in modulating a neurogenic inflammatory response induced by SP. The mechanism underlying this action is probably related to the vasodilator activity of VIP.

Animals↗
PubMed1987

The effect of substance P on the regional lymph node antibody response to antigenic stimulation in capsaicin-pretreated rats.

The undecapeptide substance P (SP) contained in primary afferent nerves is thought to mediate that part of the neurogenic inflammatory response consisting of vasodilation and plasma extravasation. This response is diminished in rats pretreated as neonates with the neurotoxin capsaicin. It is not known whether primary afferent nerves influence cellular responses of the immune response to antigenic stimulation. Using 6- to 12-wk-old Sprague-Dawley rats pretreated as neonates with capsaicin, we examined the regional lymph node response to a s.c. antigenic stimulus of sheep red blood cells. The number of cells secreting antigen-specific antibody in these animals was reduced by more than 80% using direct and indirect plaque assay methods. The reduced antibody response in capsaicin-pretreated animals was reversed by a s.c. infusion of SP given over a 4-hr period at the injection site immediately after antigen stimulation. This response had a threshold at approximately 1.0 X 10(-5) M SP. SP1-7 (1.0 X 10(-5) M) was without effect but an infusion of SP5-11 (1.0 X 10(-5) M) reversed the effects of capsaicin treatment indicating a carboxyl-terminal effect of SP. The results suggest that the reduced response of capsaicin-treated animals to an antigenic stimulus is due to an effect of capsaicin on the SP-containing primary afferent nerves rather than a toxic effect of capsaicin on the immune system.

Animals↗
PubMed1987

Substance P induces chemotaxis of neutrophils in normal and capsaicin-treated rats.

Primary afferent unmyelinated nerves modulate the inflammatory response to injury through a process known as neurogenic inflammation. The undecapeptide Substance P is contained in many of these nerves and therefore may be an important mediator of the response. Treatment of neonatal rats with capsaicin permanently destroys primary afferent unmyelinated nerves and depletes the skin and other organs of Substance P. These animals have a reduced capacity to mount an inflammatory response to injury. We examined the ability of Substance P to chemo-attract neutrophils from normal rats and rats treated as neonates with capsaicin. Substance P was shown to cause normal rat neutrophils to chemotact at an optimum concentration of 5 X 10(-5)M. Equivalent chemotaxis was observed in neutrophils from rats pretreated as neonates with capsaicin. Substance P did not increase chemokinesis. These in vitro results support the view that the reduced neurogenic inflammatory response seen in capsaicin-pretreated rats is not due to a direct toxic effect of capsaicin on neutrophils, but may be due to a decreased availability of neurally derived Substance P at the site of injury.

Animals↗
PubMed1987

Neurogenic plasma extravasation in response to mechanical, chemical and thermal stimuli.

Nociceptors at distal terminals of unmyelinated primary afferent nerve fibres mediate neurogenic inflammation. Most studies have examined only the neurogenic inflammatory response to non-physiological antidromic electrical nerve stimulation. It has not been possible to determine whether polymodal nociceptors mediate the response to physiological stimulation with mechanical, chemical and thermal stimuli. In this study we have induced plasma protein extravasation to stimulation with wool fabric (81 +/- 9 micrograms/mL), bradykinin (86 +/- 8 micrograms/mL) and heat (111 +/- 16 micrograms/mL) in perfused vacuum-induced blisters on the rat hind footpad. These values represent significant increases over the protein concentration of 30 micrograms/mL (p less than 0.005; p less than 0.001; p less than 0.001, respectively; n = 6 to 8 for each group). Plasma extravasation was significantly reduced for each stimulus modality (p less than 0.001; p less than 0.05; p less than 0.01, respectively) in animals pretreated as neonates with capsaicin, demonstrating that part of the response is neurogenically mediated. It is concluded that neurogenic inflammation to polymodal physiological stimuli occurs in the rat through capsaicin-sensitive primary afferent nerve fibres.

Animals↗
PubMed1987

Measurement of flare responses in patients with pain.

Pain is a sensory and emotional experience and, as such, is always subjective. However, for many patients pain results from stimulation of nociceptors in somatic structures. Polymodal nociceptors also mediate flare responses to noxious stimuli. In this study skin flare responses overlying the painful region in patients with pain from degenerative spine disease (16), cancer (12) and osteomyelitis (1) were examined, and compared with control areas in the same patients. Flares were induced with capsaicin (0.2 g/L in 70% ethanol) and the area was measured by planimeter after 30 minutes of exposure to the chemical. Patients with chronic pain had reduced flare responses over the pain site compared with control areas (p less than 0.1; Wilcoxon two-sample test). There was no difference between patients with acute on chronic pain and with chronic pain alone. Acute pain alone produced an increased flare response. The results suggest increased nociceptor activity in acute pain and reduced activity in chronic pain. This may reflect sensitisation and desensitisation of the nociceptor, as has been demonstrated in experimental studies in animals.

Adult↗
PubMed1987

The effects of capsaicin denervation on leucocyte and complement components of the inflammatory response.

Primary afferent unmyelinated nerves containing substance P modulate the inflammatory response to injury through a process known as neurogenic inflammation. Rats treated as neonates with capsaicin, to destroy these nerves permanently, have a reduced capacity to mount an inflammatory response as measured by swelling or plasma extravasation. In this study we examined some aspects of the immunological response to injury in capsaicin-treated rats. One question addressed was whether changes in the inflammatory response are due to abnormal innervation or to a direct toxic effect of capsaicin. It was observed that the histological appearance of thymus, splenic white pulp and popliteal lymph nodes was unaltered in capsaicin-treated rats. However, there was an increase in leucocyte number in splenic red pulp. There was also an increase in the white cell numbers in the peripheral circulation (7 +/- 1 X 10(6)/mL for normal rats and 14 +/- 2 X 10(6)/mL in capsaicin-treated rats, p less than 0.001, Student's t-test). This affected all white cell subgroups. Complement levels in capsaicin-treated rats were not different from normals and both groups showed a similar depletion 6 days following antigenic stimulation with sheep red cells. These data support the view that the reduced cellular response to injury in the capsaicin-treated rat is secondary to the effect of the chemical on afferent nerves and not to a primary toxic effect on cells of the inflammatory response.

Animals↗
PubMed1987

Increased neurogenic inflammation in fibrositis syndrome.

Mechanically induced vasodilatation or flare on the skin, known as dermatographia, is a common clinical observation in fibrositis syndrome and is thought to be a neurogenically mediated axon reflex response. In our study, mechanically and chemically induced flares were quantitated in 13 patients with fibrositis syndrome and 14 control subjects. There was a reduced threshold for chemically induced flare response and the area of flare was greater in patients compared to controls, although there was a wide range of responses in both groups. There was also a significant positive correlation between mechanically and chemically induced flares, and the number of tender points in all subjects correlated with the size of the chemically induced flare. We suggest that exaggerated neurogenic inflammatory responses in patients with fibrositis syndrome reflect increased activity of polymodal nociceptors of unmyelinated primary afferent nerves. This increased receptor activity may also contribute to the pain and tenderness experienced by these patients.

Adolescent↗
PubMed1987

Neurogenic flare responses in chronic rheumatic pain syndromes.

Chronic rheumatic pain syndromes such as the fibrositis syndrome, 'whiplash' syndrome, low back pain syndrome and regional pain syndrome are common clinical disorders of unknown cause. The presence of tender points in predictable anatomical locations is essential to their diagnosis. Exaggerated dermatographia or flare response to mechanical stimulation is also a commonly observed physical finding. Dermatographia is thought to be a local axon reflex mediated phenomenon, and, as such, is a component of the neurogenic inflammatory response. Because neurogenic inflammation may be mediated by polymodal nociceptors we examined the flare response to topical capsaicin, a chemical method of stimulating local axon reflexes, in 12 patients with chronic rheumatic pain syndromes and in 10 controls. There was a significant correlation (rs = 0.61; p less than 0.01) between the area of flare induced by mechanical stimulation and the area of flare induced by chemical stimulation for all subjects. Patients with chronic rheumatic pain syndromes had a lower threshold for capsaicin-induced flare responses compared with controls. They also had larger flares at capsaicin concentrations of 0.02 and 0.033 mg/mL (p less than 0.05) applied as 20 microL aliquots over 30 minutes. It is concluded that neurogenic flare responses are increased in patients with chronic rheumatic pain syndromes.

Afferent Pathways↗
PubMed1986

Neurogenic inflammation caused by wool fabric in the rat; possible mediation by substance P.

We have measured plasma extravasation in response to stimulation of the rat hind footpad with wool fabric. The stimulus was delivered using a constantly weighted disc of wool rotating at 4 revolutions per minute for 30 min on the base of blisters induced by vacuum. The protein content of prestimulated blister base perfusate was 38 +/- 2 micrograms/ml in a 30-min collection. With stimulation this increased to 80 +/- 10 micrograms/ml (P less than 0.001; Student's paired t-test). No increase in plasma extravasation was observed in adult animals pretreated as neonates with capsaicin indicating that the plasma extravasation observed was neurogenically mediated. Plasma extravasation was also observed with substance P added to the perfusate. The threshold for substance P-induced plasma extravasation was 2 X 10(-11) mol/30 min. These results suggest that neurogenic inflammation induced by the mechanical stimulus of wool fabric may be mediated by substance P. This reaction may be involved in wool-induced prickle and itch noted in some individuals.

Animals↗
PubMed1986

Immunoreactive substance P release from skin nerves in the rat by noxious thermal stimulation.

We have examined by radioimmunoassay the substance P (IR-SP) content of superfusate obtained from skin blisters in the anesthetized rat. The blisters were produced on the footpad using a vacuum pump, and the blister base was superfused with tyrode solution. Continuous release of IR-SP was approximately 100 pg/h from the innervated footpad but was considerably reduced when the footpad had been surgically denervated 10-14 days previously. The IR-SP content was markedly increased in the innervated footpad following a local noxious heat stimulus of 50 degrees C applied for 30 s at 5-min intervals for 1 h. The results support the proposal that SP is a mediator of neurogenic inflammation induced by noxious skin heating.

Animals↗
PubMed1986

Effects of age on the axon reflex response to noxious chemical stimulation.

The axon reflex flare response to noxious stimulation of the skin is mediated by polymodal nociceptors of "C" fibre primary afferent nerves. Topical application of capsaicin initiates such a flare. The mediator of the response is presumed to be substance P. In this study we examined the flare response to topical capsaicin (1g/L in 70% alcohol for 30 minutes; n = 220) and the substance P content of autopsied skin (3mm punch biopsy; n = 14). The area of the flare response was measured by tracing a Leitz ASM probe onto traced flare outlines. Skin was extracted in acetic acid and acetone and substance P measured by radio-immunoassay. Skin thickness was also measured in parallel biopsy specimens. The flare response decreased with increasing age at sites examined on the trunk and proximal extremities (for the trapezoid ridge r = -0.41; p less than 0.001). The substance P content of skin also decreased with age at those sites examined (for the cubital fossa r = -0.57; p less than 0.05). There was no relationship between age and skin thickness. The results demonstrate decreased activity of the axon reflex mechanism with increasing age. This may be due to changes in substance P containing nerve terminal density. The importance of a reduced neurogenic inflammatory response in the pathology of ageing is unknown.

Adult↗
PubMed1986

Substance P in human hypothalamus.

The undecapeptide substance P (SP) is found in widely dispersed areas of the brain. Recently, in experimental animals, a role for SP as a presumptive neuromodulator of endocrine responses has been described. Part of this role appears to be expressed at the level of the hypothalamo-pituitary axis. The distribution of SP in human hypothalamus and pituitary stalk has rarely been examined. In this study the distribution of SP was determined using radio-immunoassay and immunohistochemical methods in 7 regions of hypothalamus and the pituitary stalk in 21 autopsy samples. The SP content was greatest in the pituitary stalk (16.7 +/- 2.9 ng/mg protein) and the mediobasal hypothalamus at the level of the tuber cinereum. (8.3 +/- 1.1 ng/mg protein) compared with all other regions (range 3.7 to 6.0 ng/mg protein). Histochemical studies in 7 cases showed a dense innervation of the pituitary stalk portal vessels by substance P-containing nerve terminals. The pituitary stalk, mediobasal and lateral hypothalamus had the highest number of SP-containing neuronal perikarya. The SP content was not affected by age, sex or delay from death to freezing of tissue. The distribution of SP supports the view that the peptide is a neuromodulator of hypothalamo-pituitary endocrine function in man.

Adult↗
PubMed1985

Release of substance P from peripheral nerve terminals following electrical stimulation of the sciatic nerve.

Substance P is a putative mediator of neurogenic inflammation, where it is postulated to be released from nerve terminals in the skin in response to noxious and electrical stimulation. To demonstrate release of substance P from cutaneous nerve terminals a blister model has been established. Electrical stimulation of the sciatic nerve for 20 min at 50 V, 15 Hz, 0.5 ms, resulted in a significant increase in substance P-like immunoreactivity (SPLI) in blister fluid, which was abolished after neonatal pretreatment of rats with capsaicin. There was no increase of SPLI, following stimulation of the sciatic nerve at 4 V. There was a corresponding decrease in skin SPLI following nerve stimulation at 50 V. Characterization of blister fluid SPLI after stimulation at 50 V demonstrated a peak of immunoreactivity, which co-eluted with synthetic substance P and SPLI from rat skin. These results confirm the hypothesis that electrical stimulation results in release of substance P from nerve terminals in the skin, and therefore fulfils an important criterion of its role as a mediator of neurogenic inflammation.

Animals↗
PubMed1985

Neurogenic flare responses following topical application of capsaicin in humans.

The flare response to noxious stimulation of the skin is mediated by polymodal nociceptors of C fiber primary afferent nerves. Topical application of capsaicin initiates a flare response and burning pain. In this study, the variability of capsaicin-induced flare and pain was assessed in 220 subjects. The major factors in flare response are body site and age; more severe reactions occur in more proximal sites and in younger subjects. Larger flares were shown to be associated with greater pain. Variability is probably due to differences in the structure and reactivity of the neurovascular unit as proposed in the Lewis model of the axon reflex. It may prove possible to assess polymodal nociceptor function using topical capsaicin in disease states that affect the peripheral terminals of primary afferent nerves.

Administration, Topical↗
PubMed1985

The effect of nerve lesions on the inflammatory response to injury.

The effects of surgical denervation, capsaicin, and 6-Hydroxydopamine pretreatment on the inflammatory response to thermal injury have been investigated in the rat. Surgical denervation and capsaicin pretreatment reduced the cellular and exudative reactions to the injury. 6-Hydroxydopamine appeared to have a selective effect on the exudative reaction only. The effects of surgical denervation are partly explained by local and systemic effects of the procedure.

Animals↗
PubMed1985

Neurogenic inflammation in skin blisters.

The histology of blisters induced in rats using dry-ice or vacuum applied to the hind limb footpad has been examined by light microscopy and indirect fluorescence immunohistochemistry for substance P like immunoreactivity. The effects of sciatic nerve stimulation on plasma extravasation as determined by estimation of Evans Blue content of blister fluid has been examined. Plasma extravasation occurs in both blister types following nerve stimulation. Plasma extravasation may be induced by substance P released from nerve terminals in the blister wall. Vacuum induced blisters have less tissue and nerve damage and therefore less of an inflammatory response, but plasma extravasation is greater in thermal blisters. Blisters serve as a useful model for the study of neurogenic inflammation.

Animals↗