Effects of capsaicin on inflammation and on the substance P content of nervous tissues in rats with adjuvant arthritis

Colpaert, Françis C.; Donnerer, Josef; Lembeck, Fred

doi:10.1016/0024-3205(83)90060-7

Cited by 209 publications

(76 citation statements)

References 30 publications

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“…1). This exaggerated sensitivity probably relates to the sensitization of peripheral fibers by algogenic substances such as prostaglandins and substance P, whose levels are elevated in the sciatic nerve of arthritic rats (Colpaert et al, 1983). Electrophysiological studies of the dorsal horn and ventrobasal thalamus have provided a parallel pattern of data, with neurons therein showing a reduced reaction threshold (and an amplified response) to pressure applied to the limbs (Menetrey and Besson, 1982;Gautron and G&baud, 1983).…”

Section: Discussionmentioning

confidence: 99%

A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid systems

Millan¹,

Członkowski²,

Pilcher³

et al. 1987

J. Neurosci.

111

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Intradermal inoculation of rats at the tail base with Mycobacterium butyricum led to the gradual development of an arthritic swelling of the limbs which peaked at 3 weeks and subsided thereafter. Arthritic rats displayed a loss of body weight, hypophagia, and hypodipsia in addition to a disruption of the diurnal rhythms of ingestive behavior and of core temperature. The activity of adenohypophyseal beta- endorphin-(beta-EP) secreting corticotrophs, in contrast to prolactin- (PRL) secreting lactotrophs, was increased in arthritic rats. Indeed, hypertrophy of the adrenal glands was seen. Arthritic rats also showed an elevation in spinal cord levels of immunoreactive dynorphin (DYN), an endogenous ligand of the kappa-opioid receptor. The paws and tail of arthritic rats showed lower thresholds in response to noxious pressure (hyperalgesia), higher thresholds in response to noxious heat (hypoalgesia), and no change in their response to noxious electrical stimulation. Neither naloxone nor ICI-154, 129 (a preferential delta- receptor antagonist) modified the responses of the paw or tail to pressure. However, MR 2266 (an antagonist with higher activity at kappa- receptors) decreased thresholds to pressure in arthritic, but not control, rats; that is, it potentiated the hyperalgesia. This action was stereospecific. None of the antagonists modified the response to heat. MR 2266 did not affect the response to pressure in rats with acute inflammation produced by yeast. Thus, the potentiation of pressure hyperalgesia by MR 2266 in chronic arthritic rats is highly selective. Arthritic rats showed a reduced response to the analgesic effect of a kappa-agonist (U-50,488H), whereas the response to a mu- agonist (morphine) was enhanced. These effects were specific to nociception in that their influence upon endocrine secretion (PRL and beta-EP) was otherwise changed. The secretion of beta-EP and PRL was stimulated by both morphine and U-50,488H, and the influence of U- 50,488H upon the release of beta-EP (from the adenohypophysis) was enhanced in arthritic rats. It is suggested that polyarthritis is a complex condition entailing many changes, both behavioral and endocrinological. Further, arthritic rats cannot simply be described as “hyperalgesic”: of critical importance is the nature of the nociceptive stimulus applied. The parallel alterations in spinal cord pools of DYN and kappa-receptors (see also Millan et al., 1986) and the changes in the influence on nociception of kappa-agonists and kappa-antagonists suggest an increased activity of spinal DYN. Thus, spinal kappa- receptors may play a role in the modulation of nociception under chronic pain.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionmentioning

confidence: 99%

A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid systems

Millan¹,

Członkowski²,

Pilcher³

et al. 1987

J. Neurosci.

111

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“…For example, substance P (SP), which is primarily derived from sensory afferent unmyelinated c fibers, significantly augments the local inflammatory response (13)(14)(15)(16). Many other neuropeptides are present in sensory afferent unmyelinated c and small myelinated A-6 fibers, but their contribution to inflammation remains less well defined.…”

Section: Introductionmentioning

confidence: 99%

Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis.

Crofford

Sano²,

Karalis³

et al. 1992

J. Clin. Invest.

193

100

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Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, is also secreted in peripheral inflammatory sites, where it acts as a local proinflammatory agent. Arthritis-susceptible LEW/N rats have profoundly deficient hypothalamic CRH responses to inflammatory stimuli and other stressors. Arthritis-resistant F344/N rats, on the other hand, have a robust increase in hypothalamic CRH in response to the same stimuli. Contrasting with these hypothalamic CRH responses, we now show that CRH expression is markedly increased in the joints and surrounding tissues of LEW/N rats with streptococcal cell wall-and adjuvant-induced arthritis, whereas it is not increased in similarly treated F344/N rats and is only transiently increased in congenitally athymic nude LEW.rnu/rnu rats. Glucocorticoid treatment suppressed, but did not eliminate, CRH immunoreactivity in the joints of LEW/N rats. CRH mRNA was present in inflamed synovia, as well as in spinal cord, and inflamed synovia also expressed specific CRH-binding sites. We compared CRH expression in inflamed joints with another well-characterized proinflammatory neuropeptide, substance P (SP), and found that SP immunoreactivity paralleled that of CRH. In summary, although LEW/N rats have deficient hypothalamic CRH responses to inflammatory stimuli compared with F344/N rats, they express relatively high levels of CRH at the site of inflammation. Analogous to SP, CRH may be delivered to the inflammatory site by peripheral nerves and/or synthesized at the inflammatory site. These data provide further support for the concept that CRH not only triggers the pituitary-adrenal antiinflammatory cascade, but also functions as an antithetically active local mediator of acute and chronic inflammatory arthritis. These data also illustrate the complex interrelationships of the nervous, endocrine, immune, and inflammatory systems. (J.

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“…studies in man and laboratory animals have indicated that unmyelinated sensory neurones containing substance P (SP) may contribute to the pathogeneses of thermal injury (Saria, 1984;Yonehara et al, 1987), polyarthritis (Lembeck & Gamse, 1982), respiratory-tract irritation , etc. For example, in rats with experimental arthritis, an increase in the concentration of SP was observed in peripheral nerves with branches innervating inflamed joints (Levine et al, 1984), and administration of capsaicin to rats before or after the onset of arthritis diminished paw swelling and tenderness (Colpaert et al, 1983). Furthermore, thermal injury produced by heat stimulation at 45-55°C was found not only to excite pain afferents (Fleischer et al, 1983) but also to cause vascular protein leakage in the skin through release of SP from the peripheral endings of capsaicin-sensitivie, primary afferent neurones Yonehara et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw

Yonehara

Chen

Imai

et al. 1992

British J Pharmacology

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1 The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2 Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3 Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-', i.a.), propranolol (0.5 mg kg', i.a.), atropine (0.5 mg kg', i.a.), methysergide (0.5 mg kg', i.a.) or mepyramine (10mg kg-', i.a.) plus cimetidine (10 mg kg-', i.a.), but both were significantly inhibited by pretreatment with capsaicin (50mg kg-', s.c.).4 Spantide (1-2tgmolkg-', i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5 Intra-arterial infusion of SP (0.5 Mmol kg-', i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6 Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release. 7 We suggest that SP and its receptors are mainly responsible for the vascular response induced by stimulation of the sectioned sciatic nerve, and that small-diameter afferent fibres containing SP tonically regulate vascular tone in cutaneous microvessels.

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Effects of capsaicin on inflammation and on the substance P content of nervous tissues in rats with adjuvant arthritis

Cited by 209 publications

References 30 publications

A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid systems

A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid systems

Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis.

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw

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