Introduction

The term headache relates to the discomfort in the region of the cranial vault. It is one of the most common painful states that afflict the mankind. Pain following craniotomy is not uncommon and mainly manifests as pain in the cranial vault. Postcraniotomy (PC) pain may be present acutely after craniotomy or may be a chronic persistent headache. Acute postoperative pain is defined as pain presenting within first 24–48 h after a craniotomy. PC pain that fails to resolve beyond 2–3 months is defined as chronic PC pain. PC pain may be pulsating or pounding in nature or may have a steady and continuous character. Acute postoperative pain is mainly due to noxious stimulus arising from scalp incision and soft tissue dissection. However, a progressively worsening headache even in the absence of other features of raised intracranial pressure should raise red flags for postoperative hematomas or obstructed cerebrospinal pathways. Patients with PC pain usually are presumed to have a lower intensity of pain due to lesser number of pain receptors in dura, pain insensitivity of the brain, and reduced pain fiber density along the incision lines. However, Benedittis et al. conducted a pilot study and found that around 60% of patients with PC pain suffered from moderate to severe postoperative pain. They reported that pain was most frequent during first 48 h after surgery with maximum incidence at 12 h after surgery. Moderate to severe pain on day 1 and day 2 following craniotomy was also reported by Leslie et al. Several small prospective studies have documented a high incidence of moderate to severe PC pain. This postoperative pain if severe and untreated may lead to sympathetic stimulation and may precipitate secondary intracranial hemorrhage. A different approach to postoperative pain management has been advocated for craniotomy procedures because of the risk of severe sedation and cardiorespiratory instability. Fear of using opioids because of their wide array of side effects has led to the search for alternative analgesic options. Despite several researches in the treatment of acute pain, a gold standard for analgesic therapy in this subgroup of patients is still lacking. Several confounding variables like the use of differing intraoperative anesthetic regimens and lack of the use of standard opioid protocols, subjectivity of pain assessment techniques, and patients’ neurological status makes the study of PC pain a challenge.

Craniotomy Site

Since the pain is a consequence of surgical incision and is somatic in origin depending on the soft tissue and muscle dissection, craniotomy site is one of the most important factors affecting the incidence and severity of PC pain. Frontal craniotomies are associated with lower pain scores compared to craniotomies in other sites, whereas suboccipital and retrosigmoid craniectomies are associated with severe PC pain. Gottschalk et al. compared patients who underwent supratentorial procedures with those who underwent infratentorial procedures. On both the first and second postoperative days, patients who underwent infratentorial procedures had greater pain scores and received greater quantities of opioid and nonopioid analgesics than those who underwent supratentorial procedures. Benedittis et al. found that subtemporal and suboccipital routes had the greatest incidence of postoperative pain possibly due to dissection of the temporal muscles, splenius capitis, and cervicis.

Age

It was found that increased age was associated with lower pain scores. This is possibly as a result of a decrease in pain sensitivity associated with other age-related sensory losses such as changes in the visual and auditory systems. This loss of pain sensibility with age is termed “presbyalgos.”

Sex

There are variable responses of the affect of gender on PC pain. Gottschalk et al. reported a trend toward greater pain scores in women. On the contrary, Klimek et al. found no significant difference in the pain scores between males and females. Women report higher rates of pain than men, possibly because of greater health awareness, pain role perception, and illness orientation.

Preoperative Pain

Patients with preoperative pain suffer significantly more postoperative pain than patients without preoperative pain. Gee found that the clinical features of the postoperative headache was suggestive of a combination of tension type and “site of injury” headache overlying the surgical site.

Intraoperative Nerve Blocks

In a systematic review of nine randomized double-blinded placebo-controlled trials, Morten et al. concluded that intraoperative nerve block may provide longer lasting analgesia for about 6 h. Several other studies have shown that the intraoperative nerve block with local anesthetics is associated with reductions in postoperative pain.

Perioperative Opioids

Patients who required opioids preoperatively were more likely to report significantly greater levels of postoperative pain than those who did not require preoperative opioid analgesics. Mordhorst et al. noted that the probability of experiencing PC pain was reduced by 3% for each year of life. Morphine provided superior efficacy to codeine and tramadol.

Anesthetic Agents

Mordhorst et al. reported that maintenance of anesthesia with sevoflurane increased the probability of suffering from PC pain by 147%, whereas Benedittis et al. found no effect of anesthetic agents used on PC pain.

Use of Steroids

Mordhorst et al. found that the absence of corticosteroid use perioperatively increased the probability of PC pain by 119%.

Infiltration With Local Anesthetics

Local anesthetic scalp infiltration before surgical incision blunts the hemodynamic responses to craniotomy. The adrenaline component of the local anesthetic solution causes vasoconstriction and leads to a reduced blood loss during the skin and muscle incision during craniotomy. Various studies have shown that the scalp infiltration with 0.25% bupivacaine with 1:200,000 epinephrine blunts intraoperative hemodynamic responses and reduces postoperative pain scores. The effect may last long, even up to 48 h when ropivacaine is used as a local anesthetic, possibly through a preemptive mechanism.

The commonly used drugs for scalp block are summarized in Table 51.1 . The scalp block has the advantages of (1) ability to perform an accurate neurological assessment postoperatively, as it does not affect motor or sensory modalities; (2) decreases the frequency of rescue analgesics, in the initial postoperative phase ; and (3) decreases the PC pain scores with an action on the A, δ , and C fibers that innervate the scalp. A blunted stress response with reduced plasma cortisol and adrenocorticotropic hormone levels was noted with scalp block when compared with local infiltration with 0.5% bupivacaine. Ayoub et al. found that scalp nerve block provides a quality of transitional analgesia that is similar to that of morphine with a similar postoperative hemodynamic profile.

Opioids

The use of parenteral opioids during the intraoperative period blunts the hemodynamic and stress responses to various noxious stimuli in all neurosurgical procedures. Due to concerns of excessive sedation and respiratory depression (and subsequent carbon dioxide retention) the use of postoperative opioids is limited. The use of morphine for patient-controlled analgesia (PCA) reduces pain and does not appreciably increase nausea or vomiting. The addition of ondansetron produced no real benefit, and its PCA use cannot be justified.

Codeine phosphate can be used by oral, rectal, or intramuscular routes. Absorption via the rectal route is as rapid as that by the intramuscular route; however, the peak levels are lower with the rectal route. Although codeine has the advantage of not masking the pupillary signs (if any due to raised intracranial pressure), its traditional use is associated with inadequate analgesia.

Both adult and pediatric clinical studies have demonstrated that the efficacy of codeine is low and that it has a ceiling effect at higher doses above which there is a marked increase in the incidence of side effects. Stoneham and Walters compared intramuscular codeine phosphate with PCA using morphine. They found that there was a small, but nonsignificant, reduction in pain scores in the PCA group. There were no significant differences between the two groups with respect to nausea and vomiting, sedation score, or respiratory rate. Jellish et al. found that a dosing regimen of 1.5 mg morphine with a lockout period of 8 min did not lead to respiratory depression or reintubation. The authors suggested that the dose of morphine in 4 h should not exceed 40 mg. A double-blind comparison was done between codeine and morphine for postoperative analgesia following intracranial surgery. It was seen that a dose of 10 mg intramuscular morphine was more efficacious than 60 mg intramuscular codeine in terms of pain relief. The authors conclude that morphine is a safe alternative to codeine for analgesia after neurosurgery and has a more persistent action.

Fentanyl is a more lipophilic and faster acting drug than morphine. It has the disadvantage of having a short duration of action; however, it has the advantage of increased lucidity and patients’ comfort in the postoperative period. Morad et al. found that intravenous (IV) PCA with fentanyl effectively treats the pain of supratentorial intracranial surgery better than conventional as-needed (pro re nata) therapy. Patients in the former group did not experience any untoward events related to the self-administration of opioids. Similarly, IV PCA with fentanyl and ketorolac after craniotomy has been found to be a more effective analgesic technique, without adverse events, than the intermittent administration of analgesics. The use of transdermals in neurosurgical practice has disadvantages due to its delay of onset of action, unpredictable drug delivery, prolonged elimination half-life, and continuous absorption of fentanyl for a substantial period of time following patch removal.

Tramadol is an opioid analgesic, which acts as a weak μ-receptor agonist as well as an inhibitor of serotonin and norepinephrine reuptake. The analgesic efficacy of tramadol is lesser than that of morphine. However, it has the advantages as repeated administration does not lead to dependence. There is no ceiling effect, and the respiratory depression is rare.

Rahimi et al. showed that the use of tramadol results in better pain relief when used with narcotics and acetaminophen in addition to reducing the side effects of narcotics and decreasing the costs associated with hospitalizations. Sudheer et al., however, showed that tramadol administration resulted in more vomiting and retching, occurring in half of their study group, compared with 20% with morphine and 29% with codeine.

Nonsteroidal Antiinflammatory Drugs

While nonsteroidal anti-inflammatory drugs (NSAIDs) are efficient analgesics [cyclooxygenase 2 (COX-2) isomer], their use may lead to (1) platelet dysfunction and risk of bleeding (COX-1 isomer), (2) altered myocardial function, and (3) renal toxicity. The platelet dysfunction and elevated bleeding times can be critically perilous in neurosurgical patients. These concerns are mainly from the data collected from various studies, in patients receiving NSAIDs from a few days to several weeks or months preoperatively.

Palmer et al. followed the incidence of postoperative hematoma over a period of 5 years in 6668 neurosurgical procedures and found it to be 1.1%. Risk factors for a perioperative bleeding disorder were present in two-thirds of the patients. Administration of antiplatelet agents (aspirin and NSAIDs) was the most commonly associated risk factor. The authors found that at least 75% of these identified risk factors could potentially have been avoided or corrected.

Celecoxib, a COX-2 inhibitor at therapeutic doses, was found to have minimal effects on platelet function, when administered for 10 days. Unlike celecoxib, naproxen produced statistically significant reductions in platelet aggregation and serum thromboxane B2 levels and increased the bleeding time. However, the use of celecoxib is limited due to adverse cardiovascular events. NSAIDs are also implicated with increased perioperative blood loss. The range of increased blood loss varies from 1.57 to 2.08 times the blood loss in the control group in patients undergoing elective hip arthroplasty. It seems prudent to discontinue the use of NSAIDs prior to intracranial surgery.

N -Methyl- d -Aspartate Receptor Antagonist

N -methyl- d -aspartate (NMDA) receptor antagonists are believed to decrease pain by two mechanisms: reducing opioid tolerance and reducing central hypersensitivity. A 2004 review has shown a reduction in postoperative pain and analgesic requirement using dextromethorphan and ketamine. The effect of ketamine on neurosurgical patients has not been evaluated due to its psychotropic effects and its propensity to increase intracranial pressure. However, methadone can be used as an essential multimodal analgesic, acting as both an NMDA receptor antagonist and an opioid. Of note, since it does affect the QT interval, electrocardiographic monitoring should be indicated at the start of use and for chronic usage of the drug. Dextromethorphan may be used as an important constituent in the multimodal analgesia regimens following neurosurgical procedures.

Gabapentin

Gabapentin decreases the posterior horn neuronal hyperexcitability induced by lesions. It is believed that the antihyperalgesic properties of gabapentin are due to its binding activity to the alpha2-delta subunit of the voltage-dependent calcium channels of dorsal horn neurons, thereby reducing the influx of calcium into nerve endings and reducing neurotransmitter release. Other postulated mechanisms involve its action on monoaminergic pathways, sodium channels, the opioid system, and NMDA receptors. Türe et al. studied the effects of gabapentin on acute postoperative pain when administered several months in advance as antiepileptic prophylaxis in patients scheduled for craniotomies for supratentorial tumor resection. He found that preoperative administration of gabapentin was effective in treating acute postoperative pain to a small degree, and in decreasing postoperative analgesic consumption. However, it may contribute to delayed extubation and increase the level of sedation postoperatively.

α 2-Adrenoreceptor Agonist

Dexmedetomidine is a potent presynaptic α 2-adrenoreceptor antagonist that provides sedation and analgesia without respiratory depression. Discomfort and agitation after neurosurgical procedures can be treated with dexmedetomidine. The administration of dexmedetomidine before the completion of major inpatient surgical procedures has been shown to significantly reduce opioid requirements. However, patients receiving dexmedetomidine infusions may have delayed recovery and longer discharge times from the postanesthesia care unit.

Chronic Pain Following Craniotomy

The factors that can lead to the occurrence of chronic headache include dural traction, cervical muscle destruction, nerve entrapment, CSF leakage, or application of fibrin glue, which can lead to aseptic meningitis. Chronic headache is a common aftermath of head injury seen in a sizable proportion of patients.

Chronic PC pain can be treated using nonpharmacological or pharmacological means, or a combination of the two. The nonpharmacological methods used are transelectrical nerve stimulation, acupuncture, radiofrequency, cryoablation, or physiotherapy. The commonly used pharmacological agents for chronic postcraniotomy pain are NSAIDs, paracetamol, or narcotics (codeine, hydrocodone, and oxycodone). A combination therapy with newer antiepileptics like gabapentin, lamotrigine, topiramate, tiagabine, and sodium valproate can be used for PC chronic headaches.

Newer Prospects for Treating Postcraniotomy Pain

Electromyography may be used as an adjunct to pharmacological therapy for the treatment of PC pain. Cryotherapy has emerged as an attractive option for PC pain. Shin et al. found that patients who received cryotherapy by the application of ice bags to surgical wounds, and cold gel packs to periorbital areas, had lower pain scores, less eyelid edema, and less facial ecchymosis after craniotomy.