Biomedical subjects

K A Sluka

Publications and source records attributed to K A Sluka.

At least 19 recordsLinked to original sources

PubMed2001

The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice.

Cation channels in the DEG/ENaC family are proposed to detect cutaneous stimuli in mammals. We localized one such channel, DRASIC, in several different specialized sensory nerve endings of skin, suggesting it might participate in mechanosensation and/or acid-evoked nociception. Disrupting the mouse DRASIC gene altered sensory transduction in specific and distinct ways. Loss of DRASIC increased the sensitivity of mechanoreceptors detecting light touch, but it reduced the sensitivity of a mechanoreceptor responding to noxious pinch and decreased the response of acid- and noxious heat-sensitive nociceptors. The data suggest that DRASIC subunits participate in heteromultimeric channel complexes in sensory neurons. Moreover, in different cellular contexts, DRASIC may respond to mechanical stimuli or to low pH to mediate normal touch and pain sensation.

Acid Sensing Ion Channels↗

PubMed2001

Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia.

This study characterizes an animal model of persistent mechanical hyperalgesia induced by repeated intramuscular injections of low pH saline. Saline at pH 4, 5, 6, or 7.2 was injected twice, 2 to 10 days apart, into the gastrocnemius muscle of rats. To quantify hyperalgesia, paw withdrawal latency to radiant heat (heat hyperalgesia) and withdrawal threshold to mechanical stimuli (mechanical hyperalgesia) were measured. Two unilateral injections of low pH saline, 5 days apart, caused a pH-dependent bilateral mechanical, but not heat, hyperalgesia that lasted 30 days. Injections given 2 and 5 days apart produced a significantly greater mechanical hyperalgesia than injections given 10 days apart. Lidocaine injection into the gastrocnemius muscle or unilateral dorsal rhizotomy, 24 h after the second injection (pH 4), had no effect on the contralateral mechanical hyperalgesia. Minimal histopathology was observed in the injected muscle, and changes were similar between groups injected with pH 4 and pH 7.2. Thus, this new model of widespread, chronic muscle-induced pain is unrelated to tissue damage and is not maintained by continued primary afferent input from the site of injury.

Animals↗

PubMed2001

Reduction in inflammation-induced sensitization of dorsal horn neurons by transcutaneous electrical nerve stimulation in anesthetized rats.

Transcutaneous electrical nerve stimulation (TENS) is utilized to treat a variety of painful conditions. Inflamed animals present with an increased response to noxious stimuli, i.e., hyperalgesia, at the site of injury (primary hyperalgesia) and outside the site of injury (secondary hyperalgesia). Further, following acute inflammation, dorsal horn neurons show an increased responsiveness to peripherally applied stimuli, which has been termed sensitization. Previous studies demonstrate a reduction in dorsal horn neuron activity following TENS treatment in normal animals and a reduction in primary and secondary hyperalgesia in acutely inflamed animals. The purpose of this study was to examine the effects of TENS on dorsal horn neurons sensitized by acute inflammation. Extracellular recordings from wide dynamic range (WDR), high threshold (HT) and low threshold (LT) dorsal horn neurons in anesthetized rats were assessed for spontaneous activity, responses to innocuous and noxious mechanical stimulation and receptive field size. Responses were measured before and 3 h after induction of inflammation, and immediately and 1 h after application of either high (100 Hz) or low (4 Hz) frequency TENS (motor intensity, pulse duration = 100 microseconds). TENS was applied to the inflamed paw to encompass the receptive field of the neuron for 20 min. WDR and HT dorsal horn neurons sensitized to mechanical stimulation after induction of inflammation. Application of either high or low frequency TENS to the inflamed paw reduced both innocuous and noxious evoked responses of WDR and HT dorsal horn neurons immediately and 1 h after treatment with TENS. Comparison of responses after TENS with baseline responses showed that the evoked responses in the majority of WDR and HT cells returned to or fell below baseline responses. TENS had no effect on responses of LT neurons. In summary, central neuron sensitization is reduced by TENS and may underlie the reduction in hyperalgesia observed after treatment with TENS.

Action Potentials↗

PubMed2001

A novel transverse push-pull microprobe: in vitro characterization and in vivo demonstration of the enzymatic production of adenosine in the spinal cord dorsal horn.

Adenosine produces analgesia in the spinal cord and can be formed extracellularly through enzymatic conversion of adenine nucleotides. A transverse push-pull microprobe was developed and characterized to sample extracellular adenosine concentrations of the dorsal horn of the rat spinal cord. Samples collected via this sampling technique reveal that AMP is converted to adenosine in the dorsal horn. This conversion is decreased by the ecto-5'-nucleotidase inhibitor, alpha,beta-methylene ADP. Related behavioral studies demonstrate that AMP administered directly to the spinal cord can reverse the secondary mechanical hyperalgesia characteristic of the intradermal capsaicin model of inflammatory pain. The specific adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) inhibits the antihyperalgesia produced by AMP. This research introduces a novel microprobe that can be used as an adjunct sampling technique to microdialysis and push-pull cannulas. Furthermore, we conclude that AMP is converted to adenosine in the dorsal horn of the spinal cord by ecto-5'-nucleotidase and subsequently may be one source of adenosine, acting through adenosine A(1) receptors in the dorsal horn of the spinal cord, which produce antihyperalgesia.

5'-Nucleotidase↗

PubMed2001

Knee joint mobilization reduces secondary mechanical hyperalgesia induced by capsaicin injection into the ankle joint.

Joint mobilization is a treatment approach commonly used by physical therapists for the management of a variety of painful conditions. However, the clinical effectiveness when compared to placebo and the neurophysiological mechanism of action are not known. The purpose of this study was to establish that application of a manual therapy technique will produce antihyperalgesia in an animal model of joint inflammation and that the antihyperalgesia produced by joint mobilization depends on the time of treatment application. Capsaicin (0.2%, 50 microl) was injected into the lateral aspect of the left ankle joint and mechanical withdrawal threshold assessed before and after capsaicin injection in Sprague-Dawley rats. Joint mobilization of the ipsilateral knee joint was performed 2 h after capsaicin injection for a total of 3 min, 9 min or 15 min under halothane anaesthesia. Control groups included animals that received halothane for the same time as the group that received joint mobilization and those whose limbs were held for the same duration as the mobilization (no halothane). Capsaicin resulted in a decreased mechanical withdrawal threshold by 2 h after injection that was maintained through 4 h. Both 9 and 15 min of mobilization, but not 3 min of mobilization, increased the withdrawal threshold to mechanical stimuli to baseline values when compared with control groups. The antihyperalgesic effect of joint mobilization lasted 30 min. Thus, joint mobilization (9 or 15 min duration) produces a significant reversal of secondary mechanical hyperalgesia induced by intra-articular injection of capsaicin.

Animals↗

PubMed2001

Nonpharmacological treatments for musculoskeletal pain.

BACKGROUND: Several types of physical therapy are used in the management of painful musculoskeletal disorders. These treatment modalities can be broadly categorized as electrotherapy modalities (e.g., transcutaneous electrical nerve stimulation), acupuncture, thermal modalities (e.g., moist heat, ultrasound), manual therapies (e.g., manipulation or massage), or exercise. Within each of these broad categories significant variations in treatment parameters are possible. OBJECTIVE: To consider the evidence base for each of these main categories of physical therapy in the management of musculoskeletal pain. METHOD: To consider the available evidence related to clinical effectiveness and then to review evidence from basic science studies evaluating potentially therapeutic effects of the various therapies. RESULTS: There seems to be evidence from basic science research to suggest that many of the therapies could have potentially therapeutic effects. However, there appears to be limited high-quality evidence from randomized clinical trials to support the therapeutic effectiveness of several of the therapies. CONCLUSIONS: There is some preliminary evidence to support the use of manual therapies, exercise, and acupuncture in the management of some categories of musculoskeletal pain. Limitations of the existing research base are discussed and recommendations for areas of future research are provided.

Acupuncture Therapy↗

PubMed2001

Blockade of opioid receptors in rostral ventral medulla prevents antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS).

Although transcutaneous electrical nerve stimulation (TENS) is used extensively in inflammatory joint conditions such as arthritis, the underlying mechanisms are unclear. This study aims to demonstrate an opiate-mediated activation of descending inhibitory pathways from the rostral ventral medulla (RVM) in the antihyperalgesia produced by low- (4 Hz) or high-frequency (100 Hz) TENS. Paw withdrawal latency to radiant heat, as an index of secondary hyperalgesia, was recorded before and after knee joint inflammation (induced by intra-articular injection of 3% kaolin and carrageenan) and after TENS/no TENS coadministered with naloxone (20 microg/1 microl), naltrindole (5 microg/1 microl), or vehicle (1 microl) microinjected into the RVM. The selectivity of naloxone and naltrindole doses was tested against the mu-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) (20 ng, 1 microl) and the delta2-opioid receptor agonist deltorphin (5 microg, 1 microl) in the RVM. Naloxone microinjection into the RVM blocks the antihyperalgesia produced by low frequency (p < 0.001), but not that produced by high-frequency TENS (p > 0.05). In contrast, naltrindole injection into the RVM blocks the antihyperalgesia produced by high-frequency (p < 0.05), but not low-frequency (p > 0.05) TENS. The analgesia produced by DAMGO and deltorphin is selectively blocked by naloxone (p < 0.05) and naltrindole (p < 0.05), respectively. Thus, the dose of naloxone and naltrindole used in the current study blocks mu- and delta-opioid receptors, respectively. Hence, low-frequency and high-frequency TENS produces antihyperalgesia by activation of mu- and delta-opioid receptors, respectively, in the RVM.

Analgesics, Opioid↗

PubMed2000

Effect of varying frequency, intensity, and pulse duration of transcutaneous electrical nerve stimulation on primary hyperalgesia in inflamed rats.

OBJECTIVES: To examine the effect of varying frequency, intensity, and pulse duration of transcutaneous electrical nerve stimulation (TENS) on primary hyperalgesia (increased response to a noxious stimuli) to heat and mechanical stimuli induced by carrageenan paw inflammation in rats. DESIGN: Inflammation was induced by injection of 3% carrageenan into the hindpaw. Two frequencies (high, 100 Hz; low, 4 Hz), 2 intensities (high, motor; low, sensory), and 2 pulse durations (100 microsec, 250 microsec) were applied for 20 minutes to the inflamed paw. The paw withdrawal latency (PWL) to radiant heat, threshold to mechanical stimuli, and spontaneous pain-related behaviors were measured before and 4 hours after induction of inflammation, after TENS, and at 8, 12, and 24 hours after inflammation. A 3-factor (frequency, intensity, pulse duration) repeated-measures (time) design was used to analyze the changes in PWL. Mechanical threshold and spontaneous pain-related behaviors were compared for frequency, intensity, and pulse duration with a Kruskal-Wallis analysis of variance. RESULTS: For changes in PWL to heat, there was an effect for time (p = .0001) and frequency (p =.0001), but not for intensity (p = .45) or pulse duration (p = .21). For changes in mechanical threshold, there was also an effect for frequency (p = .007), but not for intensity (p = .055) or pulse duration (p = .058), after treatment with TENS. High-frequency TENS significantly reduced the primary hyperalgesia to heat and mechanical stimuli when compared with controls receiving no TENS or treatment with low-frequency TENS. High-frequency motor TENS also reduced spontaneous pain-related behaviors for 1 day after treatment. CONCLUSION: High-frequency TENS reduces primary hyperalgesia to heat and mechanical stimuli for up to 1 day after treatment. In contrast, low-frequency TENS is ineffective in reducing primary hyperalgesia. Varying intensity or pulse duration had no effect on the degree of antihyperalgesia produced by high-frequency TENS.

Animals↗

PubMed2000

Low frequency TENS is less effective than high frequency TENS at reducing inflammation-induced hyperalgesia in morphine-tolerant rats.

Both transcutaneous electrical nerve stimulation (TENS) and morphine are commonly used for relief of pain. Extensive research has been done on the effectiveness of each of these two methods for pain relief when given independently. However, very little literature exists examining the effectiveness of their combined use. Systemically administered morphine activates mu opioid receptors and when administered for prolonged periods results in analgesic tolerance. Low (4 Hz) and high (100 Hz) frequency TENS activate mu- and delta-opioid receptors, respectively, It is thus possible that TENS would be less effective in morphine-tolerant subjects. The current study investigated the effectiveness of high- and low-frequency TENS in the reversal of hyperalgesia in inflamed rats that were morphine-tolerant. Morphine tolerance was induced by subcutaneous implantation of morphine pellets over 10 days. Knee joint inflammation was induced by injection of kaolin and carrageenan into the knee joint cavity. Secondary heat hyperalgesia was tested by measuring the paw withdrawal latency to radiant heat (1) before pellet implantation (either morphine or placebo), (2) after pellet implantation and before inflammation, (3) after inflammation and (4) after TENS. Both high (100 Hz) and low (4 Hz) frequency TENS caused nearly 100% inhibition of secondary hyperalgesia in animals receiving placebo pellets. In contrast, the hyperalgesia in morphine-tolerant animals with knee joint inflammation was unaffected by low frequency TENS but fully reversed by high frequency TENS. These results suggest that patients who are tolerant to morphine may respond better to high frequency TENS than to low frequency TENS.

Animals↗

PubMed1999

Reduction of pain-related behaviors with either cold or heat treatment in an animal model of acute arthritis.

OBJECTIVE: To assess the effects of heat and cold on quantifiable pain behaviors in an animal model of arthritis that minimizes the motivational-affective component of pain. DESIGN: The effects of superficial heat (40 degrees C) and cold (4 degrees C) on pain behaviors in rats with knee joint inflammation were tested before and after induction of inflammation and after treatment with heat or cold. SUBJECTS: Joint inflammation was induced in male Sprague-Dawley rats by intra-articular injection of the knee joint with 3% kaolin and 3% carrageenan. MAIN OUTCOME MEASURES: Withdrawal latency to heat applied to the paw (PWL) assessed secondary hyperalgesia; spontaneous pain behaviors assessed degree of weight bearing/ guarding; and joint circumference assessed joint swelling. RESULTS: Cold treatment of the inflamed knee joint significantly reversed the PWL immediately after treatment (p = .003) without affecting spontaneous pain behaviors orjoint circumference. In contrast, heat treatment produced a small but significant decrease in spontaneous pain behaviors (p = .03) without affecting PWL or joint circumference. CONCLUSION: Acute arthritic pain can be treated with either superficial heat for reducing guarding or with cold for reducing pain or hyperalgesia outside the injury site.

Acute Disease↗

PubMed1999

Spinal blockade of opioid receptors prevents the analgesia produced by TENS in arthritic rats.

Transcutaneous electrical nerve stimulation (TENS) is commonly used for relief of pain. The literature on the clinical application of TENS is extensive. However, surprisingly few reports have addressed the neurophysiological basis for the actions of TENS. The gate control theory of pain is typically used to explain the actions of high-frequency TENS, whereas, low-frequency TENS is typically explained by release of endogenous opioids. The current study investigated the role of mu, delta, and kappa opioid receptors in antihyperalgesia produced by low- and high-frequency TENS by using an animal model of inflammation. Antagonists to mu (naloxone), delta (naltrinodole), or kappa (nor-binaltorphimine) opioid receptors were delivered to the spinal cord by microdialysis. Joint inflammation was induced by injection of kaolin and carrageenan into the knee-joint cavity. Withdrawal latency to heat was assessed before inflammation, during inflammation, after drug (or artificial cerebral spinal fluid as a control) administration, and after drug (or artificial cerebral spinal fluid) administration + TENS. Either high- (100 Hz) or low- frequency (4 Hz) TENS produced approximately 100% inhibition of hyperalgesia. Low doses of naloxone, selective for mu opioid receptors, blocked the antihyperalgesia produced by low-frequency TENS. High doses of naloxone, which also block delta and kappa opioid receptors, prevented the antihyperalgesia produced by high-frequency TENS. Spinal blockade of delta opioid receptors dose-dependently prevented the antihyperalgesia produced by high-frequency TENS. In contrast, blockade of kappa opioid receptors had no effect on the antihyperalgesia produced by either low- or high-frequency TENS. Thus, low-frequency TENS produces antihyperalgesia through mu opioid receptors and high-frequency TENS produces antihyperalgesia through delta opioid receptors in the spinal cord.

Animals↗

PubMed1998

Increased spinal release of excitatory amino acids following intradermal injection of capsaicin is reduced by a protein kinase G inhibitor.

Second messengers have been shown to play a role in the release of neurotransmitters presynaptically in several brain regions and cell types. This study was designed to test the hypothesis that the increased release of aspartate and glutamate that occurs after injection of capsaicin is dependent on activation of the cAMP and the cGMP transduction cascades. A microdialysis fiber was implanted into the dorsal horn of the spinal cord for collection of extracellular fluid and for administration of drugs to the spinal cord. Dialysate samples were collected before and after injection of capsaicin and after infusion of inhibitors of protein kinase G (PKG; KT5823) or protein kinase A (PKA; H89). KT5823, H89, or artificial cerebrospinal fluid (ACSF; control) were administered after injection of capsaicin to reduce the increased release of aspartate and glutamate. At the time of injection of capsaicin, there is an increase in release of aspartate (191+/-21%) and glutamate (194+/-14%). This increased release is maintained through 2.5 h for both glutamate and aspartate at approximately 125% to 150%. The increase in aspartate and glutamate concentrations that occurs after capsaicin injection was reduced back to baseline after spinal infusion of the PKG inhibitor, KT5823. Blockade of PKA had no effect on the increased release of aspartate and glutamate. Thus, the current data support a role for the cGMP-PKG pathway in the control of neurotransmitter release in vivo.

Alkaloids↗

PubMed1998

The effects of SDZ NKT 343, a potent NK1 receptor antagonist, on cutaneous responses of primate spinothalamic tract neurones sensitized by intradermal capsaicin injection.

Substance P, acting through neurokinin I receptors, is involved in the processing of nociceptive information in the spinal cord. Sensitization of spinothalamic tract neurons occurs to low-intensity stimuli following capsaicin injection. The current study tested the effects of the novel neurokinin I receptor antagonist, SDZ NKT 343, on the sensitization of spinothalamic tract cells by capsaicin in monkeys. Spinothalamic tract cells from the lumbar enlargement with receptive fields in the hindpaw were isolated and recorded before and after intradermal injection of capsaicin. The background activity and responses to brushing, pressing and pinching the skin were assessed. Thirty minutes after capsaicin injection there was an increase in background activity and responses to brush and pressure applied to the receptive field. Infusion of SDZ NKT 343 (for 30-45 min) significantly reversed the increased response to brushing without affecting the increased background activity or the increased response to pressure. Thus, blockade of neurokinin 1 receptors reduces the sensitized responses to innocuous mechanical stimuli but not to noxious mechanical stimuli.

Action Potentials↗

PubMed1998

Treatment with either high or low frequency TENS reduces the secondary hyperalgesia observed after injection of kaolin and carrageenan into the knee joint.

For years, physical therapists have been utilizing a variety of modalities, including transcutaneous electrical nerve stimulation (TENS), in an attempt to manage pain associated with inflammation. However, the data on clinical effectiveness is conflicting and the neurophysiological mechanism of action is not known. The purpose of this study was to investigate the effects of high and low frequency TENS on the secondary hyperalgesia that occurs after joint inflammation. Secondary hyperalgesia is thought to reflect changes in central neurons and is thus a measure of activity of central neurons. This study utilized the kaolin and carrageenan model of knee joint inflammation and measured the effects of TENS treatment on paw withdrawal latency to radiant heat (secondary hyperalgesia), spontaneous pain behaviors and joint circumference. Either high (100 Hz) or low (4 Hz) frequency TENS was applied to the knee joint for 20 min after the development of hyperalgesia. Both high and low frequency TENS resulted in a reversal of the hyperalgesia immediately following treatment. The effects of high frequency TENS lasted through at least 24 h while those of low frequency TENS lasted through 12 h. There was no effect of TENS on spontaneous pain behaviors or joint swelling when compared to controls. Thus, TENS appears to be more effective in reducing referred pain (or secondary hyperalgesia) without affecting guarding or splinting of the affected limb. Thus, clinically, the choice to use TENS may depend on patient symptoms; specifically TENS should be effective in reducing referred or radiating pain.

Animals↗

PubMed1998

Blockade of N- and P/Q-type calcium channels reduces the secondary heat hyperalgesia induced by acute inflammation.

High voltage calcium channels are implicated in nociceptive transmission after nerve injury, capsaicin or formalin injection. The purpose of this study was to investigate the role of calcium channels in secondary heat hyperalgesia associated with acute joint inflammation. After induction of acute inflammation (knee joint injection of kaolin and carrageenan), decreased paw withdrawal latency (PWL) to radiant heat (i.e., secondary heat hyperalgesia), increased guarding of the limb and increased joint circumference occurs. Spinal administration (through a microdialysis fiber placed in dorsal horn) of an N-type calcium channel blocker (MVIIA, SNX 111, ziconotide, 0.001-0.1 mM), before induction of inflammation, prevents the decrease in PWL. Treatment with SNX 111 4 hr after inflammation reverses heat hyperalgesia. A small reduction in spontaneous pain-related behaviors (guarding of the limb) occurs after pre- or post-treatment with SNX 111. Spinal blockade of P/Q-type calcium channels (with omega-agatoxin IVA) had no effect on the decrease in PWL to radiant heat when administered after induction of inflammation. However, pre-treatment with omega-agatoxin IVA prevents secondary heat hyperalgesia. omega-Agatoxin IVA has no effect on spontaneous pain-related behaviors whether administered before or after induction of inflammation. In contrast, pre or post-treatment with nifedipine (L-type calcium channel blocker, 0.01-1.0 mM), had no effect on heat hyperalgesia or spontaneous pain-related behaviors induced by acute inflammation. There were no differences in joint circumference between groups with any treatment. Thus, N-type calcium channels contribute to both the development and maintenance of secondary heat hyperalgesia while P-type calcium channels are only involved during development of hyperalgesia.

Animals↗

PubMed1997

Capsaicin-induced sensitization of primate spinothalamic tract cells is prevented by a protein kinase C inhibitor.

Protein kinase C (PKC) has been shown to be involved in nociceptive transmission in the spinal cord. This study tested the hypothesis that induction of central sensitization in the dorsal horn by an intradermal capsaicin injection involves activation of PKC. A PKC inhibitor (NPC15437) was infused through a microdialysis fiber into the spinal cord prior to capsaicin injection. The responses of spinothalamic tract (STT) cells were recorded before and after infusion of NPC15437, and after injection of capsaicin. STT cells show an increased background activity and increased responses to innocuous stimuli following capsaicin injection while responses to heat are decreased. Spinal infusion of the PKC inhibitor, NPC15437, had no effect on background activity or responses to peripherally applied stimuli prior to capsaicin injection. However, NPC15437 prevented the sensitization of cells to weak mechanical stimuli (brush and pressure) that occurs following capsaicin injection. NPC15437 had no effect on the increased background activity or decreased responses to heat stimuli induced by capsaicin injection, suggesting alternative mechanisms for these responses. These data suggest that PKC is important for the development of central sensitization to peripheral mechanical stimuli.

Animals↗

PubMed1997

Inhibitors of G-proteins and protein kinases reduce the sensitization to mechanical stimulation and the desensitization to heat of spinothalamic tract neurons induced by intradermal injection of capsaicin in the primate.

Intradermal injection of capsaicin results in sensitization of spinothalamic tract cells to brushing and pressure applied to the cutaneous receptive field in anesthetized monkeys. A significant increase in background activity also occurs immediately after capsaicin injection that lasts for at least 2 h. A 40-50% decrease in the response to noxious heat stimuli is also observed following capsaicin injection. This study investigated the spinal role of second messengers by extracellularly recording from spinothalamic tract cells and delivering inhibitors of second messenger pathways to the spinal cord by microdialysis. Blockade of protein kinases with the general protein kinase inhibitor, H7 (5.0 mM, n = 6), reduced the sensitization of the cells to brush and pressure. Blockade of protein kinase C with NPC15437 (10.0 mM, n = 10) reduced the increased background activity and the increased responses to brush. Blockade of protein kinase A with H89 (0.01 mM, n = 9) was most effective. H89 reduced the background activity, the increased responses to brush and press, and reversed the decreased response to noxious heat stimuli. Blockade of G-proteins with the general G-protein inhibitor, GDP-beta-S (1.0 mM, n = 9), reduced the background activity and the responses to brush and pressure without affecting the decreased response to heat. Thus, multiple intracellular messengers appear to be involved in the processing of central sensitization induced by activation of C-fibers following intradermal injection of capsaicin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1997

Blockade of calcium channels can prevent the onset of secondary hyperalgesia and allodynia induced by intradermal injection of capsaicin in rats.

Intradermal capsaicin injection in humans results in primary hyperalgesia to heat and mechanical stimuli applied near the injection site, as well as secondary mechanical hyperalgesia (increased pain from noxious stimuli) and mechanical allodynia (pain from innocuous stimuli) in an area surrounding the site of primary hyperalgesia. This study in rats tested the hypothesis that the secondary hyperalgesia and allodynia observed following intradermal injection of capsaicin was dependent upon activation of voltage sensitive calcium channels in the spinal cord. Responses to application of von Frey filaments of 10 mN and 90 mN bending forces were tested in all rats before and after injection of capsaicin into the plantar surface of a hindpaw. Animals were pretreated with L-type (nifedipine), N-type (omega-conotoxin GVIA) or P-type (omega-agatoxin IVA) calcium channels blockers through a microdialysis fiber implanted in the spinal dorsal horn prior to the injection of capsaicin. None of the calcium channel blockers had any affect on normal sensory or motor responses. However, all three blockers dose dependently prevented the development of secondary mechanical hyperalgesia and allodynia. The threshold to mechanical stimulation with von Frey filaments was also increased significantly in animals treated with these calcium channel blockers when compared to articial cerebrospinal fluid control animals. These data suggest that calcium channels are important for the development of mechanical hyperalgesia and allodynia that occurs following capsaicin injection.

Animals↗