Biomedical subjects

T Kauppila

Publications and source records attributed to T Kauppila.

At least 19 recordsLinked to original sources

PubMed2000

Cold exposure enhances tactile allodynia transiently in mononeuropathic rats.

A laser and erythrosin-B-induced sciatic nerve injury decreases thresholds of a mechanically induced paw withdrawal reflex and enhances cold-induced withdrawal behavior of the affected limb. Exposure of the affected paw to a normally innocuous cold stimulus results in a transient decrease in the threshold of the mechanically evoked paw withdrawal reflex in neuropathic but not in intact rats. The present data suggest that in an experimental neuropathic state a normally innocuous cold stimulus may further sensitize spinally mediated withdrawal reflexes to stimuli of another stimulus modality, in this case, to innocuous tactile stimuli. Therefore, testing mechanical allodynia in neuropathic rats immediately after testing cold allodynia may produce artifactual results.

Animals↗

PubMed2000

Photochemically-induced ischemic injury of the rat sciatic nerve: a light- and electron microscopic study.

Lesion of presumably ischemic origin of the rat sciatic nerve was induced photochemically by laser irradiation combined with systemic administration of a photosensitizing organic dye, erythrosin B. We have studied the pathologic features of the nerve after the photochemical insult with light- and electronmicroscopy and related them to behavioral signs of neuropathic pain. At the irradiated nerve site, occlusion of blood vessels was seen and the vessels were packed with aggregated thrombocytes, fibrins and deformed erythrocytes, supporting the notion that photochemical reaction caused intraneural ischemia. The degree of the nerve injury at the center of irradiation was related to the duration of the laser exposure. Brief irradiation (30 seconds) only caused identifiable injury to myelinated fibers, whereas longer irradiation (2 minutes) caused greater injury to myelinated and unmyelinated fibers, characterized by extensive axonal degeneration and demyelination. The rats irradiated for 2 minutes, but not 30 seconds, exhibited neuropathic pain-like behaviors, expressed as mechanical and cold allodynia. The nerve injury was most severe 7 days after ischemia and regeneration of both myelinated and unmyelinated fibers was observed 3 months later. The nerve caudal to the irradiation exhibited Wallerian degeneration 7 days after the insult, whereas at 10 mm proximal to the irradiation the nerve was largely normal. It is thus concluded that photochemically induced intraneural ischemia caused injury to both myelinated and unmyelinated fibers, with myelinated fibers being more susceptible. However, the development of neuropathic pain-like behaviors may require injury to the unmyelinated fibers.

Animals↗

PubMed1999

Allodynia induced by regenerating axons is not positively correlated with degree of autotomy in the rat.

We studied in the rat whether the incidence of autotomy correlated positively with severity of tactile allodynia induced by regenerating axons. Before transection and surgical repair of the sciatic nerve, the status of sensory function was studied by stimulating mechanically the central part of the plantar paw with von Frey-hairs. Thereby we determined the threshold to evoke the hindpaw withdrawal reflex. One and 2 months after the nerve transection and repair, the thresholds of the traumatized paws were lower than the pre-trauma thresholds. The contralateral paw withdrawal thresholds did not change during the follow-up time. The results indicated that regenerating axons may cause tactile allodynia and that the severity of this allodynia does not correlate positively with the incidence of autotomy. We found no contralateral allodynia after nerve transection and repair.

Animals↗

PubMed1999

Behavioural measures of depression and anxiety in rats with spinal nerve ligation-induced neuropathy.

The behaviour of rats with spinal nerve ligation-induced neuropathic pain was studied using tests developed to measure depression and anxiety. Adult male Sprague-Dawley rats were tested with the open field test, elevated plus maze, two compartment test and forced swimming test. Spontaneous motility was measured in a photocell observation box. Mechanical sensitivity was tested with von Frey hairs and cold sensitivity with the acetone drop test. The L5-6 spinal nerves were ligated or a sham operation was performed and the rats were followed for 2 weeks before the same set of tests were repeated. Most of the neuropathy operated rats had mechanical and cold allodynia. With post-injury there was a significant decrease in the activity in the open field test and motility box tests, when compared with the pre-injury results. In the elevated plus maze test there was a significant reduction in the motility, but there was no change in the time spent in the closed wings. In the two compartment test there were no significant differences between the pre- and post-injury results. There were no differences between the rats with spinal nerve ligation injury and the sham operated rats in any of the tests. The results were also comparable when rats that developed a high degree of neuropathy were compared with the rats with low degree of neuropathy and the sham operated group. In conclusion, spinal nerve ligation injury of the spinal nerves L5-6 induces mechanical and cold allodynia, but it does not seem to produce general suffering or measurable anxiety to the animals. Furthermore, tests for anxiety and depression were not able to predict which animals were vulnerable to express symptoms of neuropathic pain after nerve injury.

Animals↗

PubMed1998

Influence of spinalization on spinal withdrawal reflex responses varies depending on the submodality of the test stimulus and the experimental pathophysiological condition in the rat.

The influence of midthoracic spinalization on thermally and mechanically induced spinal withdrawal reflex responses was studied in the rat. There were three experimental groups of rats: healthy controls, rats with a spinal nerve ligation-induced unilateral neuropathy, and rats with a carrageenan-induced inflammation of one hindpaw. Tail flick response was induced by radiant heat. Hindlimb withdrawal was induced by radiant heat, ice water, and innocuous or noxious mechanical stimulation of the paw. Prior to spinalization, spinal nerve ligated and carrageenan-treated animals had a marked unilateral allodynia and hyperalgesia. Spinalization tended to induce a facilitation of noxious heat-evoked reflexes. This spinalization-induced facilitation was stronger on tail than hindlimb withdrawal. Spinalization-induced skin temperature change did not explain the facilitation of noxious heat-evoked reflexes. In contrast, spinal withdrawal responses induced by noxious cold or mechanical stimulation were significantly suppressed following spinalization. The spinalization-induced facilitatory effects as well as inhibitory ones on spinal reflexes were enhanced in inflamed/neuropathic animals. The results indicate that the tonic descending control of spinal nocifensive responses varies depending on the submodality of the test stimulus, the segmental level of the reflex (tail vs. hindlimb), and on the pathophysiological condition.

Animals↗

PubMed1998

Capsaicin-induced impairment of tactile spatial discrimination ability in man: indirect evidence for increased receptive fields in human nervous system.

The effects of capsaicin was investigated on vibration detection thresholds, touch detection thresholds, mechanically-evoked pain thresholds, two-point discrimination ability, and ability to detect roughness of different stimulation surfaces in the left hands of human volunteers in a double-blind controlled study. Capsaicin cream induced allodynia to mechanical stimulation in both primary and secondary area of hyperalgesia. Capsaicin impaired two-point discrimination ability, and reduced the ability to detect differences of the roughness of various stimulation surfaces only within the capsaicin treated area (area of primary hyperalgesia). These changes were not seen after placebo cream. We conclude that experimental inflammation and related pain impairs spatial discrimination ability which could be due to increases in the receptive fields of neurons in the peripheral and central nervous system (CNS).

Adult↗

PubMed1998

Dextromethorphan potentiates the effect of morphine in rats with peripheral neuropathy.

Neuropathic pain responds poorly to opioids. We now report that combination of systemic morphine (2 mg/kg) and dextromethorphan (45 mg/kg), a clinically available antitussive with NMDA-antagonist properties, markedly alleviated mechanical and cold allodynia-like behavior in a rat model of peripheral mononeuropathy. Neither drug produced a significant effect on its own at these doses. The anti-allodynic effect of morphine plus dextromethorphan was reversed by naloxone. The present results suggest that a combination of NMDA-antagonist and opiates might be effective in treating neuropathic pain. Furthermore, the effect of this drug combination is mainly mediated via opioid receptors.

Analgesics, Opioid↗

PubMed1998

Carrageenan-induced changes in spinal nociception and its modulation by the brain stem.

Carrageenan was used to study inflammation-induced changes in spinal nociception and its brain stem modulation in the pentobarbitone-anesthetized rat. Carrageenan was administered intraplantarly into one hindpaw 2 h before the start of electrophysiological single unit recordings of wide-dynamic range (WDR) neurons of the spinal dorsal horn. Carrageenan produced a significant leftward shift in the stimulus-response function for mechanical stimuli, whereas that for noxious heat stimuli was short of statistical significance. Conditioning electrical stimulation in the rostroventromedial medulla (RVM) significantly attenuated noxious heat-evoked, but not mechanically evoked, responses to spinal dorsal horn WDR neurons in the control (contralateral) side. However, in the carrageenan-treated side RVM stimulation had no significant effect on mechanically or noxious heat-evoked responses. Following direct spinal administration of neuropeptide FF (NPFF), noxious heat-evoked responses, but not mechanically evoked responses, were attenuated by RVM-stimulation also in the carrageenan-treated side. This selective NPFF-induced enhancement of brain stem-spinal inhibition was not reversed by naloxone. The results indicate that carrageenan-induced inflammation significantly changes the response properties of spinal nociceptive neurons and their brain stem-spinal modulation. During inflammation, NPFF in the spinal cord produces a submodality-selective potentiation of the antinociceptive effect induced by brain stem-spinal pathways, independent of naloxone-sensitive opioid receptors.

Animals↗

PubMed1998

The effect of a selective alpha2-adrenoceptor antagonist on pain behavior of the rat varies, depending on experimental parameters.

Effects of atipamezole, an alpha2-adrenoceptor antagonist, in various acute pain tests were studied in the rat. Atipamezole (at doses > or = 0.1 mg/kg I.P.) and idazoxan, another alpha2-adrenoceptor antagonist (2.5 mg/kg, I.P.), increased licking latency in the hot-plate test. Bilateral administration of atipamezole (10 microg) into the locus coeruleus did not increase licking latency in the hot-plate test. Medetomidine (an alpha2-adrenoceptor agonist; 1-3 mg/kg) or repeated pre-exposures to the testing apparatus reversed the effect of atipamezole (1.5 mg/kg) in the hot-plate test. Atipamezole also increased the latency to mechanically induced licking/biting response at a dose of 1.5 mg/kg, but not at lower doses. In the heat-induced tail-flick test, in contrast, atipamezole at doses of 0.1 and 1.5 mg/kg produced a medetomidine-reversible decrease of response latencies. This facilitation of the tail-flick response disappeared if the intensity of the heat stimulus was high. At a dose range from 0.03 to 1.5 mg/kg atipamezole did not significantly alter the paw withdrawal latency to noxious mechanical stimulation, nor pain behavior in the formalin test. Responses to nociceptive spinal dorsal horn neurons were not modulated by atipamezole (1 mg/kg) in anesthetized spinalized rats. The results indicate that an alpha2-adrenoceptor antagonist may have variable effects in behavioral pain tests, depending on habituation of the experimental animals to the testing conditions, the dose of the drug, the type of behavioral response and the submodality or the intensity of the noxious test stimulus. The atipamezole-induced changes in pain behavior observed in this study may rather be explained due to action on motor expression of pain than due to modulation of nociception.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1998

Correlation between autotomy-behavior and current theories of neuropathic pain.

The past 10 years have brought several new experimental models with which to study chronic neuropathic pain in animals. Consequently, our knowledge about the mechanisms subserving neuropathic pain in humans has improved. However, the first animal model that was used for studying this type of chronic pain was the autotomy-model which can still be considered as a useful tool for pain studies. The present review assesses some of the similarities and differences between autotomy-model and more recent models of experimental traumatic mononeuropathy. In addition, it considers some of the similarities between the results obtained in clinical studies and in autotomy studies.

Animals↗

PubMed1997

Spinalization increases the mechanical stimulation-induced withdrawal reflex threshold after a sciatic cut in the rat.

The purpose of the present study was to establish whether supraspinal structures modulate mechanical 'adjacent hyperalgesia'. After a chronic sciatic cut, the paw withdrawal threshold to mechanical stimulation was lower, and the latency of noxious radiant heat-induced withdrawal reflex was shorter at the traumatized side than at the intact side. Then the rats were spinalized, and the withdrawal threshold to mechanical stimulus increased at the injured side, but the withdrawal latency induced by noxious heat decreased at the intact side. No side differences between the injured and the intact side could be detected after spinalization. Thus supraspinal structures may participate in maintenance of mechanically evoked paw withdrawal reflex after a sciatic injury.

Animals↗

PubMed1997

Use of paper for treatment of a peripheral nerve trauma in the rat.

Reinnervation of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves.

Animals↗

PubMed1996

Sciatic nerve section induces mechanical hyperalgesia in skin adjacent to the deafferented region in rats: lack of correlation with autotomy behavior.

We have studied the development of cutaneous hypersensitivity in the innervation area of the saphenous nerve and autotomy behavior in rats after unilateral sciatic nerve section. Hypersensitivity was assessed by stimulating the saphenous area with mechanical (von Frey hairs and analgesimeter), cold (immersion) or heat (immersion or radiant heat) stimuli 10 days after sciatic nerve section. We did not observe any hypersensitivity to thermal stimulation or weak mechanical stimulation produced by von Frey hairs. A significant decrease in withdrawal threshold to intense mechanical pressure produced by analgesimeter was observed, indicating the possible presence of mechanical hyperalgesia. Eleven of 17 rats had started autotomy at this time, but there was no correlation between the presence of autotomy and mechanical hyperalgesia. It is concluded that in our experimental setting, only mechanical hyperalgesia was present 10 days after axotomy. Moreover, autotomy behavior and adjacent hyperalgesia may be triggered by different mechanisms.

Animals↗

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↗

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↗

PubMed1994

Nerve resuturation decreases autotomy in the rat.

Effects of different kinds of nerve lesions on denervation-induced self-mutilation (autotomy) was studied in the rat. Four different types of lesion were used: nerve transection, nerve transection combined with ligation and extirpation of the distal part of the transected nerve, nerve resuturation with a microsurgical technique, and lidocaine treatment after transection but before and during nerve resuturation. To determine the degree of nerve regeneration, the extensor muscles of the ankle joint were prepared and weighed after the follow-up period. If the transected nerves were resutured the incidence and severity of autotomy decreased significantly when compared to the transection+ligation-treated rats. The pretreatment with lidocaine did not further decrease the autotomy behavior of the rats whose nerves were resutured. In those rats who performed autotomy the early onset of self-mutilation correlated positively with a moderate, but not high or low, degree of restoration of the muscle weight. The present results suggest that autotomy can be decreased with good surgical techniques after nerve resuturation.

Animals↗