Pain
-
Transcutaneous electrical nerve stimulation (TENS) is a treatment for pain that involves placement of electrical stimulation through the skin for pain relief. Previous work from our laboratory shows that repeated application of TENS produces analgesic tolerance by the fourth day and a concomitant cross-tolerance at spinal opioid receptors. Prior pharmacological studies show that blockade of cholecystokinin (CCK) receptors systemically and spinally prevents the development of analgesic tolerance to repeated doses of opioid agonists. ⋯ Spinal blockade of CCK-A or CCK-B receptors blocked the development of tolerance to high and low frequency TENS, respectively. In the same animals we show that spinal blockade of CCK-A receptors prevents cross-tolerance at spinal delta-opioid receptors that normally occurs with high frequency TENS; and blockade of CCK-B receptors prevents cross-tolerance at spinal mu-opioid receptors that normally occurs with low frequency TENS. Thus, we conclude that blockade of CCK receptors prevents the development of analgesic tolerance to repeated application of TENS in a frequency-dependent manner.
-
Both cyclooxygenase-1 and -2 are expressed in the spinal cord, and the spinal COX product prostaglandin E(2) (PGE(2)) contributes to the generation of central sensitization upon peripheral inflammation. Vice versa spinal COX inhibition is considered an important mechanism of antihyperalgesic pain treatment. Recently, however, COX-2 was shown to be also involved in the metabolism of endocannabinoids. ⋯ During established inflammation all COX inhibitors reduced release of spinal PGE(2) almost equally but only the COX-2 inhibitor prevented breakdown of 2-AG. The reversal of spinal hyperexcitability by COX-2 inhibitors was prevented or partially reversed by AM-251, an antagonist at the cannabinoid-1 receptor. We conclude that inhibition of spinal COX-2 not only reduces PG production but also endocannabinoid breakdown and provide evidence that reversal of inflammation-evoked spinal hyperexcitability by COX-2 inhibitors is more related to endocannabinoidergic mechanisms than to inhibition of spinal PG synthesis.
-
Randomized Controlled Trial
Diffuse analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers.
We investigated the analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) in two models of experimental pain in healthy volunteers. Two studies were carried out in parallel in two groups of 26 paid healthy volunteers. The effects of active or sham rTMS (frequency, 10Hz; intensity, 80% resting motor threshold) applied to the right M1 or DLPFC were compared in a double-blind randomized cross-over design. ⋯ By contrast, the second study showed that rTMS of M1 or DLPFC had no significant effect on the threshold or recruitment curve of the nociceptive flexion RIII reflex. Our findings demonstrate that unilateral rTMS of M1 or DLPFC induces diffuse and selective analgesic effects in healthy volunteers. The lack of effect on the RIII reflex suggests that such analgesic effects may not depend on the activation of descending inhibitory systems.
-
This study examines the relationship between the severity of painful temporomandibular joint disorders (TMD) symptoms and current tobacco use in patients evaluated at a specialized orofacial pain clinic. Medical records, including responses to the Chronic Pain Grading Scale (CPGS), from 606 consecutive patients evaluated at the Mayo Clinic orofacial pain clinic with TMD by RDC-TMD criteria were retrospectively reviewed. Univariate analyses were performed comparing tobacco users and non-users. ⋯ In the subset of subjects who lacked a myofascial component of pain (N=333) this difference remained significant in the adjusted analysis (adjusted OR=4.56, 95% CI 1.46-14.24). Current tobacco use was associated with unfavorable demographic background variables and more pain interference in subjects with TMD presenting to a specialized orofacial pain clinic. These effects were more pronounced in cases where myofascial pain was not present.