Pain perception, brain and consciousness.

The brain-mind debate presents two principal streams of thought: materialist (brain and mind are different aspects of the same extremely complex "thing") and dualist (brain and mind are two independent things). Originating as a signal of damage transmitted to the thalamus, a warning message becomes perceived pain when the thalamus sends it to, and it is integrated by, the cerebral and cingulated cortices. In addition to various endogenous and exogenous physical factors that may affect (or even inhibit) the perception of pain, pain perception may be modulated, that is, enhanced or inhibited, by cognitive and emotive factors whose origins and existence are principal elements in the brain-mind debate. Studying the perception and modulation of pain provides an excellent heuristic model for studying the brain-mind debate and, in turn, an understanding of the brain-mind debate may offer new possibilities in pain therapy.

Relationship between MPQ and VAS in 962 patients. A rationale for their use.

BACKGROUND: 1) To analyse the information provided both by the Visual Analogue Scale (VAS) and by the McGill Pain Questionnaire (MPQ) in a cross-sectional study with patients affected by different kinds of pain and to study the relationship between VAS and MPQ scores in the same patient sample. METHODS: 962 patients affected by different kinds of pain (i.e. neuropathic pain, acute post-traumatic pain, chronic musculo-skeletal pain, headache, and cancer pain) were enrolled into the study during the first visit for pain management. The horizontal 10cm VAS and the Italian version of the MPQ were administered. RESULTS: VAS scores proved to be significantly lower in acute post traumatic and in chronic musculo- skeletal pain compared to headache and neuropathic pain. VAS scores were signi- ficantly higher in neuropathic pain compared to cancer pain. MPQ total score (Pain Rating Index, PRI) related to neuropathic pain was significantly higher than scores reported in the other pain groups, with the exception of cancer pain. Cancer pain MPQ total score was higher than acute post-traumatic and chronic musculo-skeletal PRI pain scores. Different patterns of MPQ dimensions emerged within each pain group. The association between VAS and PRI, analysed by means of stepwise multiple regression analyses was significantly different among the groups (p<0.0001). The percentage of VAS variance explained by MPQ PRI score ranged from 6% (headache) to 32% (neuro-pathic pain). CONCLUSIONS: Several differences emerged among the pain groups. VAS and MPQ resulted to address pain aspects only partially overlapping. In some clinical conditions (headache and cancer) the MPQ can provide more detailed and clinically useful information about patients' pain experience.

Effect of somatostatin on beta-endorphin release in rat experimental chronic inflammation.

The aim of the present study was to investigate the effect of somatostatin administration in arthritic rats. Inflammation was induced by daily interplantar injection of 100 microl of Freund's complete adjuvant into the left hind paw of the rat. Arthritis developed 20 days following the first injection and was stable in the inoculate paw. Arthritic rats were treated interplantarly with somatostatin (5 or 10 microg) or with indomethacin (100 microg) daily for 14 days. Inflammatory response was studied at 12 h, 7 and 14 days following drug administration. The effect of somatostatin was determined by local (into popliteal lymph nodes) and systemic production of beta-endorphin. Our results showed that somatostatin treatment significantly increased beta-endorphin levels in the blood and lymphocytes from popliteal lymph nodes. Greater efficiency was seen when 5 microg instead of 10 microg of somatostatin was used. A significant decrease of absolute leukocytosis was observed at the 14th day following somatostatin administration. Moreover, a significant reduction of plasmatic beta-globulins at 12 h and the 7th day and of plasmatic alpha2-globulins at the 14th day was observed after the beginning of somatostatin treatment.

The effect of somatostatin on experimental inflammation in rats.

UNLABELLED: The aim of the present study was to investigate the effect of somatostatin administration on experimentally induced inflammation in rats. Inflammation was induced by the intraplantar injection of carrageenan (50 microL) into the hind paw of the rat. Animals were treated intraplantarly with somatostatin in a volume of 50 microL at different doses (2.5, 25, and 250 ng, 10 microg). The inflammatory response was studied 120, 180, and 240 min after drug administration. The antinociceptive effect of somatostatin was determined by using the Randall and Selitto test and by local production of beta-endorphin from lymphocytes obtained from popliteal lymph nodes. Data show that small doses of somatostatin were the most effective in reducing hyperalgesia. Moreover, our results show that somatostatin treatment significantly increased beta-endorphin in lymphocytes from popliteal lymph nodes. The secretion of opioid peptides, which enhance analgesia, could be stimulated by locally administered somatostatin. IMPLICATIONS: Acute pain because of intraplantar inflammation induced in rats by carrageenan injection was significantly reduced by small-dose, local administration of somatostatin, which possibly favors beta-endorphin release as a mechanism. These results may have implications regarding treatment of pain conditions associated with an inflammatory response.

Influence of inhalational, neuroleptic and local anaesthesia on lymphocyte subset distribution.

We previously demonstrated that anaesthetics affect leukocyte response by inhibiting lymphocyte capping and metabolism and the phagocytic activity of neutrophils in some experimental models. In the present study, we investigated the effects of the clinical use of three different types of anaesthesia on lymphocyte subset distribution and activity: inhalational anaesthesia (isoflurane), a neuroleptoanalgesia, or local anaesthesia was used in patients submitted to the same operation (hysterectomy). At time 0 (before administering the anaesthesia) and at 10 min and 48 h from the start of the operation, heparinized blood was obtained from each of the 30 patients studied; three lymphocyte subpopulations were isolated (CD4+, CD8+ and CD19+). Cell number was identified for each lymphocyte subset, and (as an indication of cellular function) the intracellular contents of ATP and cAMP were evaluated by luminescence methods. The relevant results for each of the 3 anaesthetic methods were as follows: i) treatment with isoflurane induced a significant reduction in the number and function of CD4+ cells at 10 min, which was reversed at 48 h; a functional but not reversible decrease of CD19+ cells was obtained, ii) treatment with neuroleptic drugs induced a significant progressive functional impairment of CD4+ and CD19+ cells, and iii) local anaesthesia caused a significant functional impairment of CD8+ cells at 48 h and a significant functional impairment of CD19+ cells at 10 min and 48 h.

Centrally administered neuropeptide Y fails to increase food intake but enhances hypoalgesia in spontaneously hypertensive rats.

The effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY1-36) on food intake and pain sensitivity in hot plate test were studied in spontaneously hypertensive rats (SHRs) and in normotensive Wistar-Kyoto (WKy) rats. In satiated SHRs NPY1-36 failed to significantly increase intake at doses that produced a strong effect in satiated WKy rats (0.25-1.25 nmol). Conversely, both NPY1-36 and the C-terminal fragment NPY13-36, a putative selective agonist for the Y2-receptor for NPY, enhanced the spontaneously occurring hypoalgesia of SHRs, having no effect in WKy rats. The present results indicate that the NPY central systems involved in the control of regulatory functions are differently tuned in SHRs and WKy rats, suggesting possible involvement of these systems in the genesis of hypertension.

Pain, analgesia, and stress: an integrated view.

The different theories on the neuroanatomical substrate of pain have been revised in the frame of new concepts on the intercellular communication in the central nervous system. In fact, it has recently been proposed that two kinds of electrochemical transmission exist in the brain: the first one, called wiring transmission (WT), uses neuronal chains (neuronal plasma membranes and synaptic contacts), whereas the second one, called volume transmission (VT), uses the extracellular fluid as physical substrate. The old concept of a separate system of afferents and central cells that constitute the pain mechanism is no more longer tenable. To reach a better understanding of the psychophysiological basis of pain, we should consider a view where WT and VT cooperate within neuronal systems functionally affected by the pervading modulatory action of endocrine signals.

A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain.

Antidepressant drugs are increasingly used in the management of chronic pain. They are mainly prescribed for cancer-related pain and central pain, e.g. phantom or stump pain, post-herpetic neuropathy. However, no controlled clinical trials have validated their in either pathology. Thus, physicians still do not know whether antidepressants are really effective and which might be best. It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself. To verify both the analgesic effect of tricyclic antidepressants, and the possible relationship between their antidepressant effect and the relief of central pain, we carried out a randomized, within-patient (cross-over) placebo-controlled study in patients suffering from central pain. The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo (p less than 0.0001). Within the antidepressants tested, chlorimipramine, a blocker of serotonin reuptake, is significantly more effective (p less than 0.0001) than notriptyline, a blocker of noradrenaline reuptake. Finally, the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression.

Pattern reversal visual evoked potentials (VEP-PR) in migraine subjects with visual aura.

Twenty patients with migraine with visual aura, aged 19 to 55 years (2 men and 18 women) were studied by the method of Visual Evoked Potentials (VEP). The control group consisted of an equal number of healthy subjects, comparable for age and sex. The most important finding in our study is that migraine patients with visual prodromata have a significantly longer P100 latency than the subjects of control group. These modifications of the VEP-PR could indicate, as other investigators have pointed out, that there are some special metabolic conditions and abnormalities of neuromediators during and between attacks.

The descending inhibitory pathways. Their role in analgesia, after consideration of specific spinal adrenergic involvement.

The four main descending pathways - from the cortex, the diencephalon, the mesencephalon and the pontobulbar structures - are briefly examined with regard to their role as regulatory systems with an overall inhibitory action processing the afferents to the spinal cord. Sketches are given of the possible analgesic properties in the selective gating of C and Ad nociceptive afferences. The involvement of neuronal subpopulations in the spinal cord presenting alpha-2 and alpha-1 receptors, their hypothetic role in certain reactive analgesic processes, and their coactivation are mentioned briefly.