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A Pertovaara

Publications and source records attributed to A Pertovaara.

At least 55 records · Page 3Linked to original sources
PubMed1997

Differential effects of noxious conditioning stimulation of the cheek by capsaicin on human sensory and inhibitory masseter reflex responses evoked by tooth pulp stimulation.

In this study, we investigated whether selective activation of nociceptive primary afferent fibers by capsaicin would induce modulations on tooth-pulp-evoked sensory or inhibitory masseter reflex responses in healthy human subjects. The contribution of central N-methyl-D-aspartate (NMDA) receptor mechanisms in capsaicin-induced effects on sensory or reflex responses was evaluated by dextromethorphan, an NMDA-receptor antagonist. The inhibitory masseter reflex was evoked by electrical stimulation (constant current, single pulses) of the upper incisor while the subject was biting at 10% of his maximal force. The sensation of the tooth pulp stimulation was evaluated by visual analogue scale (VAS). The magnitude, duration, and the the latency of the reflex were determined by bite force measurements. The inhibitor masseter reflex could be induced by non-painful tooth pulp stimulation, and the inhibition was enhanced as a function of increasing stimulus intensity. Capsaicin (1%) applied topically to the skin of the cheek produced a spontaneous burning pain sensation. During capsaicin treatment, the VAS ratings for the sensation induced by tooth pulp stimulation were significantly reduced, whereas no significant changes were found in the tooth-pulp-induced masseter reflex responses. Double-blind treatment with dextromethorphan at a dose of 100 mg (= the highest does without side-effects) had no effect on sensory or reflex responses. These data indicate that noxious stimulation of the facial skin by capsaicin induces differential effects on tooth-pulp-evoked sensory and inhibitory masseter reflex responses: Sensory responses are strongly attenuated, while masseter reflex responses are not significantly changed. Dextromethorphan at a clinically applicable dose does not influence tooth-pulp-evoked sensory or reflex responses or their modulation by capsaicin. Furthermore, the lack of modulation of the masseter reflex response by capsaicin differs from the capsaicin-induced enhancement of a nocifensive limb flexion reflex described earlier.

Administration, Cutaneous↗
PubMed1996

Lidocaine in the rostroventromedial medulla and the periaqueductal gray attenuates allodynia in neuropathic rats.

In the present study we attempted to find out if the rostroventromedial medulla (RVM) or the periaqueductal gray (PAG) might contribute to chronic allodynia induced by unilateral ligation of two spinal nerves in the rat. Lidocaine was microinjected in the RVM or PAG and allodynia was quantitatively determined by measuring the hindlimb withdrawal thresholds to mechanical stimulation of the paw. For comparison, lidocaine was also injected systemically (s.c.). Lidocaine in the RVM produced a dose-related (20 and 40 micrograms) antiallodynic effect. Lidocaine (20 micrograms) in the PAG produced identical antiallodynic effect as in the RVM. With systemic administrations of lidocaine, a considerably higher dose (> > 40 micrograms) was needed to produce a significant antiallodynic effect. Naloxone, an opioid-antagonist (1 mg/kg s.c.), did not attenuate the antiallodynic effect of lidocaine in the RVM. An antiallodynic dose of lidocaine (20 micrograms) in the RVM or the PAG did not influence the withdrawal response in the unoperated hindlimb nor the heat-induced tail-flick reflex. The results indicate that the RVM and the PAG have a facilitatory influence on the spinal segmental mechanisms underlying chronic allodynia. The selective attenuation of allodynia induced by lidocaine in the RVM and the PAG is independent of opiate receptors, and it can not be explained by a systemic spread of the drug.

Animals↗
PubMed1996

Influence of selective nerve fiber blocks on argon laser-induced thermal pain in the human skin.

Influence of selective nerve fiber blocks on cutaneous pain induced by short argon laser pulses was studied in healthy humans. The minimal energy per surface area needed to produce a pain sensation was lower with a larger stimulus surface indicating spatial summation. Both compression of the peripheral nerve innervating the stimulus site (A-fiber block) and prolonged topical treatment of the stimulus site with 1% capsaicin (a predominant block of nociceptive C-fibers) produced an elevation of the pain threshold. Prolonged capsaicin treatment produced significantly higher pain thresholds than the compression block. Magnitude of the pain threshold elevation induced by nerve blocks varied depending on the area of the stimulus surface. Especially following prolonged capsaicin treatment, pain threshold elevations tended to be smaller with the larger area of the stimulus surface suggesting an enhanced spatial summation effect. Tactile thresholds were significantly elevated only by the compression block. The results indicate that nociceptive C-fibers have a significant contribution to the threshold sensation of pain induced by argon laser. Moreover, following impairment of function in nociceptive C-fibers, the spatial summation of argon laser-induced pain tends to be enhanced.

Adult↗
PubMed1996

Different roles of alpha 2-adrenoceptors of the medulla versus the spinal cord in modulation of mustard oil-induced central hyperalgesia in rats.

We attempted to determine the roles of spinal versus medullary alpha 2-adrenoceptors in modulation of central hyperalgesia in rats. Central hyperalgesia was produced by applying mustard oil (50%) to the skin of the ankle of one hindpaw. The threshold for eliciting a hindlimb flexion reflex was determined by applying a series of calibrated monofilaments to the glabrous skin of the hindpaw contralaterally (= control) or ipsilaterally to the mustard oil-treated ankle (= outside the area of primary hyperalgesia). Medetomidine (an alpha 2-adrenoceptor agonist; 1 micrograms), atipamezole (an alpha 2-adrenoceptor antagonist; 2.5 micrograms) or saline was microinjected into the lateral reticular nucleus of the medulla, the nucleus raphe magnus, or intrathecally to the lumbar spinal cord 12 min before the mustard oil treatment. Following saline injections, mustard oil produced a significant decrease of the hindlimb withdrawal threshold in the mustard oil-treated limb but not in the contralateral limb. Atipamezole in the lateral reticular nucleus produced a complete reversal of the hyperalgesia but no effect on the threshold of the intact limb. However, atipamezole in the raphe magnus nucleus or in the lumbar spinal cord did not produce a significant attenuation of the hyperalgesia. Medetomidine in the spinal cord, but not in the lateral reticular nucleus, reversed the hyperalgesia. At this dose range (up to 3 micrograms), medetomidine in the spinal cord of nonhyperalgesic control rats did not produce any significant change in the withdrawal response of hindlimbs or in the tail-flick latency. The results indicate that neurogenic inflammation induces significant plastic changes in the function of alpha 2-adrenergic pain regulatory mechanisms. In rats with mustard oil-induced central hyperalgesia, an alpha 2-adrenoceptor antagonist produces an antihyperalgesic effect due to an action on the caudal ventrolateral medulla, whereas an alpha 2-adrenoceptor agonist produces an enhanced antinociceptive effect due to a direct action on the spinal cord.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1996

Influence of skin temperature on heat pain threshold in humans.

We compared the effect of skin temperature on the critical threshold temperature eliciting heat pain with the effect of skin temperature on the response latency to the first heat pain sensation in healthy human subjects. Also, we determined the effect of the duration of a heat stimulus ramp on pain threshold. Furthermore, we determined the effect of skin temperature on mechanically induced pain. We found that the latency to the first pain sensation induced by a radiant heat stimulus was significantly decreased with an increase in the skin temperature (25-35 degrees C). However, independent of the rate of the stimulus rise (3-10 degrees C/s) and independent of the stimulus location (hairy vs glabrous skin), the threshold temperature for eliciting the heat pain sensation, determined with a contact thermostimulator, was not changed by a change in the skin temperature in the same subjects. With a fast rate of stimulus rise, a higher pain threshold was obtained than with a slow rise of stimulus temperature. However, this difference was found only with subject-controlled ascending stimuli (method of limits) but not with experimenter-controlled, predetermined stimulus ramps (method of levels). The heat pain threshold was higher in the glabrous skin of the hand than in the hairy skin of the forearm. With increasing stimulus duration (2.5-10 s), the threshold temperature eliciting the heat pain sensation was significantly decreased. The mechanically induced pain threshold was not influenced by the skin temperature. The results indicate that the critical temperature for eliciting heat pain is independent of the skin temperature in humans. However, a change in skin temperature is an important source of an artefactual change in heat pain sensitivity when the radiant heat method (latency or energy) is used as an index of pain sensitivity. With a method dependent on reaction time (the method of limits), the heat pain threshold was artefactually increased, with fast rates of stimulus rise due to the long delay of slowly conducting heat pain signals in reaching the brain. With an increase in the duration of the heat stimulus, the critical temperature for eliciting pain sensation was significantly decreased, which may be explained by central neuronal mechanisms (temporal summation).

Adult↗
PubMed1996

A noninvasive method for studying quantitatively heat-evoked nocifensive hindlimb withdrawal reflexes in lightly anesthetized rats.

We have developed a noninvasive method for studying quantitatively the magnitude of hindlimb withdrawal reflexes induced by noxious heat in lightly anesthetized rats. The amplitude, latency, and duration of the hindlimb withdrawal was determined by a very small piezoceramic device placed on the hamstring muscle while the glabrous skin of the hindpaw was stimulated using a feedback-controlled contact thermostimulator. An increase in the amplitude and duration of the withdrawal response, concomitant with a decrease in the response latency, was found with increasing stimulus temperature. The sensitivity of the method was verified using morphine, which produced a dose-related (3.5-7.0 mg/kg) attenuation of all these response components. The use of a piezoceramic device for measuring the withdrawal response provides a quantitative, noninvasive method for evaluating the magnitude of various components of the nocifensive withdrawal reflexes induced by noxious stimuli in lightly anesthetized rats.

Animals↗
PubMed1996

Medetomidine, atipamezole, and guanfacine in delayed response performance of aged monkeys.

The effects of a highly selective alpha-2 adrenergic agonist medetomidine and its antagonist atipamezole were studied on the delayed response task performance of aged monkeys. Medetomidine, at the dose of 1.0 micrograms/kg, improved the memory task performance, whereas atipamezole had no effect on the performance at any dose. It has earlier been shown that alpha-2 adrenergic agonists clonidine and guanfacine improve age-associated memory impairment, but also contradictory effects of clonidine have been reported. There is evidence that the ability of alpha-2 agonists to improve DR task performance is due to its selective action on the alpha-2A receptor subtype. Clonidine and medetomidine are much less selective than guanfacine with respect to alpha-2A and alpha-2B receptor subtypes. Therefore, we also studied the effect of guanfacine on the memory task performance of the same aged monkeys in the same testing conditions to compare the effectiveness of these two alpha-2 adrenergic compounds. Guanfacine improved memory task performance at the dose of 0.0001 mg/kg. The results indicate that alpha-2 agonists, independent of their different selectivity with respect to alpha-2A/2B receptor subtypes, are beneficial drugs in improving the performance in the delayed response task.

Adrenergic alpha-Agonists↗
PubMed1995

Can the alpha 2-adrenoceptor agonist-mediated suppression of nocifensive reflex responses be due to action on motoneurons or peripheral nociceptors?

To exclude the possibility that the suppression of nocifensive reflex responses induced by alpha 2-adrenergic agents is due to action on alpha-motoneurons or peripheral nociceptors, we studied the effect of medetomidine, an alpha 2-adrenoceptor agonist, on the monosynaptic reflex and on the primary afferent nociceptor-mediated antidromic vasodilator response in rats. Additionally, the effect on the dorsal root potential, an index of a transient excitability change in the central terminals of primary afferent fibers, was determined. Medetomidine was applied systemically at doses (100 and 300 micrograms/kg) which have proven strongly antinociceptive in previous studies. The amplitudes of a submaximal monosynaptic reflex volley or a submaximal dorsal root potential were not changed by medetomidine. Medetomidine induced a decrease of cutaneous blood flow but did not abolish the vasodilatatory response to antidromic stimulation of the sciatic nerve at C-fiber intensity as determined by the laser Doppler flow method. The results indicate that the alpha 2-adrenoceptor-mediated suppression of nocifensive reflex responses is not caused by a decreased excitability of motoneurons or peripheral nociceptors. An alpha 2-adrenoceptor agonist does not modulate the transient stimulus-evoked change in the excitability of central terminals of primary afferent fibers.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1995

Influence of selective alpha 2-adrenergic agents on mustard oil-induced central hyperalgesia in rats.

The effects of systemically administered medetomidine, an alpha 2-adrenoceptor agonist, and atipamezole, an alpha 2-adrenoceptor antagonist, on mustard oil-induced central hyperalgesia were determined in unanesthetized rats. The mechanical threshold for eliciting a hindlimb flexion reflex (a nocifensive response) was determined with a series of calibrated monofilaments. Under control conditions mustard oil produced a significant decrease of the hindlimb withdrawal threshold for mechanical stimuli applied to a distal site in the hindlimb, whereas the corresponding threshold in the (untreated) contralateral side was not changed. Medetomidine administered 12 min prior to mustard oil treatment produced a significant dose-dependent (3-30 micrograms/kg s.c.) attenuation of the mustard oil-induced threshold decrease whereas the withdrawal threshold of the contralateral (untreated) hindlimb was not changed at these low doses. The antinociceptive effect of medetomidine (10 micrograms/kg) administered 12 min prior to the mustard oil treatment was not significantly stronger than the effect of medetomidine administered immediately after the mustard oil treatment. Atipamezole at a high (1000 micrograms/kg) or a low (10 micrograms/kg) dose did not influence the mustard oil-induced threshold decrease, whereas at an intermediate dose (100 micrograms/kg) atipamezole alone had a significant antinociceptive effect on mustard oil-induced hyperalgesia. The results indicate that medetomidine produces a selective attenuation of central hyperalgesia at doses which are sub-antinociceptive in intact rats. A pre-emptive treatment with medetomidine did not produce stronger antinociception than medetomidine treatment after the development of hyperalgesia. An alpha 2-adrenoceptor antagonist, atipamezole, attenuated central hyperalgesia in a non-monotonic fashion.

Adrenergic alpha-Agonists↗
PubMed1995

Effect of cocaine on sexual behaviour in male stumptail macaques (Macaca arctoides).

The effect of cocaine (0.01-1.0 mg/kg) on sexual behaviour was studied in four male stumptail macaques (Macaca arctoides). Following drug-saline control administration, the behaviour of the male monkey with a female was observed for 30 min in two different behavioural conditions; in one of the conditions the baseline sexual activity was low, and in the other it was high (partial or complete separation of the male and the female between the sessions, respectively). The reversal of the cocaine-induced effects was attempted by haloperidol (0.003-0.01 mg/kg), a dopamine-2-receptor antagonist. Cocaine (0.1-1.0 mg/kg) produced a highly significant dose-dependent suppression in the number of ejaculations. The cocaine-induced suppression of ejaculatory behaviour was completely reversed by haloperidol. Haloperidol at the dose range used did not in itself influence ejaculatory behaviour. The effect of cocaine on grooming, nonejaculatory mounting, aggression, or perineal investigations did not reach statistical significance. The possibility that cocaine at very low doses (0.01-0.1 mg/kg) might increase sexual activity was excluded in the behavioural condition with a low basal sexual activity. The results indicate that cocaine dose-dependently suppresses ejaculatory behaviour as a result of dopamine-2-receptor-mediated mechanisms. The cocaine-induced suppression of ejaculatory behaviour might be explained by the strong rewarding effect of cocaine alone.

Animals↗
PubMed1995

An attempt to attenuate experimental pain in humans by dextromethorphan, an NMDA receptor antagonist.

Dextromethorphan (100 mg, orally), an NMDA receptor antagonist, did not significantly attenuate pain intensity or unpleasantness induced by experimental ischemia or by topical capsaicin in healthy human subjects, nor did it increase the threshold for heat pain or mechanical pain. A dose of 200 mg produced marked side effects. Thus, systemically administered dextromethorphan does not attenuate pain at clinically applicable doses in humans.

Adult↗
PubMed1995

Activation of alpha 2-adrenergic receptors decreases nerve trauma-induced afferent barrage but not autotomy.

Effects of the selective alpha 2-adrenoceptor agonist, medetomidine, on a compound volley of a tibial nerve stimulation-evoked spinal reflex, pain-induced phrenic motor responses and on postoperative neuropathic pain behavior were studied in rats. Medetomidine (0.3 mg/kg) decreased the amplitude of the compound volley recorded from peroneal nerve in response to tibial stimulation in pentobarbital (40 mg/kg) anesthetized rats. Atipamezole, an alpha 2-adrenoceptor antagonist (1.5 mg/kg) fully restored the response when given 60 min after the medetomidine administration. Pain-evoked phrenic motor responses were completely inhibited upon combination anesthesia by pentobarbital (40 mg/kg) and medetomidine (0.3 mg/kg) (PB+M) but not upon plain pentobarbital anesthesia (50 or 60 mg/kg) (PB50,PB60). To study the effect of medetomidine on postoperative neuropathic pain behavior (autotomy), transection of sciatic nerve was done under PB+M, PB50 or PB60 anesthesia. No differences between the groups were found in the postoperative pain behavior during eight-week follow up. The results show that activation of alpha 2-adrenergic receptors by medetomidine under pentobarbital anesthesia mitigates trauma-induced afferent barrage, whereas it does not reduce the subsequent autotomy.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1995

The antinociceptive action of an alpha 2-adrenoceptor agonist in the spinal dorsal horn is due to a direct spinal action and not to activation of descending inhibition.

In this electrophysiological study we tried to find out whether the spinal antinociceptive effect of a supraspinally administered alpha 2-adrenoceptor agonist is due to a direct spinal effect or to activation of descending inhibition. The responses to wide-dynamic range (WDR) neurons of the spinal dorsal horn were studied following application of medetomidine, a selective alpha 2-adrenergic agonist, into the rostroventromedial medulla (RVM) or directly onto the spinal cord of the intact and in spinal rats. The noxious electrical stimuli were applied to the ipsilateral receptive field in the plantar region of the hind paw, and responses mediated by A- and C-fibers to WDR neurons were separately evaluated. The reversal of medetomidine-induced effects was attempted by a systemic administration of atipamezole, a selective alpha 2-adrenoceptor antagonist. Medetomidine injection into the RVM produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses to WDR neurons of the spinal dorsal horn in both intact and spinal rats. Paradoxically, the spinal antinociceptive effect of supraspinally administered medetomidine was stronger in spinal rats. The A-fiber-mediated responses were significantly less attenuated by medetomidine than the C-fiber-mediated responses to the WDR neurons. Also a direct application of medetomidine onto the spinal cord produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses, and this effect was identical in intact and in spinal rats. The medetomidine doses producing spinal antinociception were considerably lower with a direct spinal application than with a supraspinal application.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-2 Receptor Agonists↗
PubMed1995

The role of alpha 2-adrenoceptors of the medullary lateral reticular nucleus in spinal antinociception in rats.

We attempted to find out the role of alpha 2-adrenoceptors of the medullary lateral reticular nucleus (LRN) in antinociception in rats. Spinal antinociception was evaluated using the tail-flick test, and supraspinal antinociception using the hotplate test. Antinociceptive effects were determined following local electric stimulation of the LRN, and following microinjections of medetomidine (an alpha 2-adrenoceptor agonist; 1-10 micrograms), atipamezole (an alpha 2-adrenoceptor antagonist; 20 micrograms) or lidocaine (4%) into the LRN. The experiments were performed using intact and spinalized Hannover-Wistar rats with a unilateral chronic guide cannula. Electric stimulation of the LRN as well as of the periaqueductal gray produced a significant spinal antinociceptive effect in intact rats. Medetomidine (1-10 micrograms), when microinjected into the LRN, produced no significant antinociceptive effect in the tail-flick test in intact rats. However, following spinalization, medetomidine in the LRN (10 micrograms) produced a significant atipamezole-reversible antinociceptive effect in the tail-flick test. In the hot-plate test, medetomidine (10 micrograms) in the LRN produced a significant atipamezole-reversible increase of the paw-lick latency in intact rats. Microinjection of atipamezole (20 micrograms) or lidocaine alone into the LRN produced no significant effects in the tail-flick test. The results are in line with the previous evidence indicating that the LRN and the adjacent ventrolateral medulla is involved in descending inhibition of spinal nocifensive responses. However, alpha 2-adrenoceptors in the LRN do not mediate spinal antinociception but, on the contrary, their activation counteracts antinociception at the spinal cord level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-2 Receptor Agonists↗
PubMed1994

Capsaicin-induced central facilitation of a sympathetic vasoconstrictor response to painful stimulation in humans.

The effect of capsaicin, a compound selectively activating nociceptive primary afferent fibers, on a centrally mediated autonomic (sympathetic) vasoconstriction response to painful peripheral stimulation was studied in healthy human volunteers. Capsaicin (1%) was applied topically to the dorsal forearm and the threshold for eliciting a vasoconstriction response in the contralateral forefinger to painful electrical or thermal stimulation of the forearm skin adjacent to or remote from the capsaicin-treated region was determined with Laser Doppler flowmetry. Capsaicin produced a significant decrease of the threshold for the vasoconstriction response to painful electrical stimulation of the area of central allodynia; i.e., the skin area located adjacent to the capsaicin-treated region in which a light touch evoked an unpleasant sensation. Capsaicin did not change the threshold for the vasoconstriction response to painful heat stimuli applied to the area of central allodynia or to painful electric stimulation applied outside the borders of the allodynic area. Heart rate, blood pressure and heart vagal tone were not modified by capsaicin. It is concluded that a selective activation of nociceptive primary afferent fibers of the skin by capsaicin produces a central submodality-dependent facilitation of an autonomic vasoconstriction response to noxious stimulation in humans. This central facilitation can be explained by segmental excitability changes of afferent interneurons at the spinal cord level.

Adult↗
PubMed1994

Influence of various experimental parameters on the incidence of thermal and mechanical hyperalgesia induced by a constriction mononeuropathy of the sciatic nerve in lightly anesthetized rats.

In the current investigation we examined a peripheral mononeuropathy induced by four loose ligatures around the sciatic nerve. The nerve was treated with lidocaine or saline before implementing the ligatures (silk or chromic gut). The latency of the hindlimb withdrawal to noxious mechanical and radiant heat stimuli was tested under light pentobarbital anesthesia 3-10 days following the surgery. A latency/threshold difference > or = 15% between the hindlimbs was considered to represent a change in the nocifensive response. The adapting skin temperature of the hindlimbs was also measured. Pieces of hindpaw skin and the sciatic nerve were taken for histological evaluation. The results indicate that the incidence of hyperalgesia induced by a constriction mononeuropathy depended on the noxious submodality tested, and that the thermal and mechanical hyperalgesia were not coupled in all cases. Use of only one test modality led to false negative results. Furthermore, mononeuropathy-induced changes in the adapting skin temperature produced a considerable number of false positive results (an artefactual hyperalgesia) when radiant heat alone was used to determine the nocifensive withdrawal latency without paying attention to the abnormality of the skin temperature. A preemptive lidocaine treatment of the sciatic nerve before the nerve ligation significantly reduced the incidence of mononeuropathy-induced hyperalgesia. The nerve ligation material (silk vs chromic gut) was not a significant factor for the development of hyperalgesia induced by a constriction injury of a peripheral nerve. In histological evaluation the constriction injury-induced damage of the sciatic nerve was verified, and the inflammatory reaction caused by chromic gut was not stronger than that caused by silk ligatures. In general, immunohistochemical staining for substance P decreased whereas that for VIP increased. The results support the hypothesis that ligation-induced mechanical trauma and the afferent barrage induced by it, especially during the perioperative period, plays an important role in the development of postoperative hyperalgesia.

Adaptation, Physiological↗